Atlas of Macromolecules for MolviZ.Org (Atlas.MolviZ.Org) Suggestions to Eric Martz. Last updated: 2016. Atlas of Macromolecules by Eric Martz is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Click on any image for more information.

Contents Lesson Plans Enzymes Soluble Proteins (Not Enzymes) Signal Cascade Proteins (Intracellular) Structural & Motility Proteins Calcium-Binding Proteins Lipid Bilayers & Water Integral Membrane Proteins Myristoylated Proteins DNA, RNA Proteins Complexed to Nucleic Acids (Transcription Factors, Polymerases, Nucleosome, Ribosome, etc.) Virus Capsids Virus Components Immune System & Defense Molecules (Antibody, MHC, etc.) Toxins Carbohydrates Magnificent Molecular Machines Unusual Tertiary/Quaternary Structures Intrinsically Disordered/Natively Unstructured Proteins Animated Morphs of Conformational Changes Amyloids Evolutionary Conservation History: Earliest Crystallographic Structures Other Browsable Lists of Molecules Notes Acknowledgements Atlas Update History

STRAIGHTFORWARD
• Lysozyme, human, complexed to inhibitor, (1965-1994). Hen egg white lysozyme was the first enzyme structure solved crystallographically (see history). Catalytic mechanism, 2001.
• Trypsin (porcine pancreatic) complexed to soybean trypsin inhibitor, (1998).
• Carboxypeptidase A complexed with inhibitor, (1992).
• Acetylcholinesterase complexed with huperzine inhibitor, (1993-1997). In FirstGlance: Views tab, Solid, then rotate until you can see the inhibitor deep down in the catalytic gorge.
• Lipase, (1994). See animation of catalytic pocket opening.
• HIV protease with inhibitor, 2002). This type of inhibitor is what is saving the lives of people infected with HIV (More).
• Angiotensin-converting enzyme complexed with inhibitory drug lisinopril (licensed for treating hypertension), (2003). Such inhibitors were developed without knowing the target protein structure, and on the assumption of mechanistic homology with carboxypeptidase A. This structure showed little if any such homology, but rather structural (but not sequence) homology to a family of zinc metalloproteases.
• Intramembrane protease: see Integral Membrane Proteins.
   
  CHALLENGING
• Animated simulation of the process of HIV protease inhibitor Ritonavir binding to the protease. This simulation is fictional, but chemically possible. The simulation was generated, starting with (1997), by pulling the inhibitor out of the "side" of the protease with concurrent real-time energy minimization by molecular mechanics using the (now apparently defunct) Sculpt energy minimization software package. The animation can be viewed in the article Molecular Playground/HIV Protease Inhibitor: there, press the button play animation.
• Calcineurin, a serine/threonine phosphatase with two metals in its catalytic site, a myristoylated regulatory chain with four bound calcium ions, complexed with the immunosuppresant drug FK506 and FK506-binding protein, (1995). What is the state of the catalytic site?
• Glutamine synthetase, a twelve-chain homo-dodecamer, (1995). See the overview of this molecule at Molecule of the Month.
• Particulate methane monooxygenase converts methane to methanol: (2005). Can you guess the environment in which this enzyme functions by examining its surface polarity? Understanding the mechanism of this metallo-enzyme may facilitate the development of synthetic catalysts useful in alternative energy strategies.

STRAIGHTFORWARD
• Inositol 1,4,5-triphosphate bound to the ligand-binding domain of the endoplasmic-reticulum-membrane-associated calcium release channel, (2002).
• Phytochrome (definition) chromophore-binding domain with covalently bound biliverdin, (2005). Surprisingly, the structure contains a knot. (Knots are quite rare in proteins.) The knot appears to stabilize the region near the chromophore. More about this and other knots in proteins.
  
  
• Postsynaptic density master scaffolding protein, under structural proteins.

STRAIGHTFORWARD
• Myoglobin, oxy, (1958-1980). The first protein structure solved crystallographically (see history).
• Myoglobin, deoxy, with all hydrogen atoms! (2000). What was the experimental method? (See Note #1.)
• Hemoglobin, deoxy, (1968-1992).
  See the hemoglobin tutorial at MolviZ.Org in various languages.
• Insulin, (1982-1992).
• Green fluorescent protein, (1997).
• Bone morphogenetic protein complexed with its inhibitor Noggin, described as "back-to-back butterflies" (Nature 420:613), (2002). These secreted proteins control events in embryonic morphogenesis. Don't miss the cystine knots! To see the "butterfly" you will need to view the biological unit.

  See (under other categories)

• Calmodulin

  CHALLENGING

• Sickle cell hemoglobin (dimer of tetramers bound via mutant valine), (1985). See the hemoglobin tour at MolviZ.org.

Anthrax Toxins
• Review of the anthrax disease and its toxins, Mock & Fouet, Ann. Rev. Med. 55:647, 2001. See also Nature's Focus on Anthrax.
• Anthrax protective antigen, PA ( 1997) transports the lethal and edema factors through the cell membrane. The full length PA 735 AA chain, PA83, is cleaved to form the active fragment PA63, which forms heptamers. The publication linked to 1ACC describes the PA monomer and heptmer, but the 4.5A heptamer model was not deposited in the PDB. Robert Liddington kindly provided the with permission to share it for educational purposes.
• Anthrax lethal factor alone (2001), and complexed to its target MAPKK2, (2001). Note that 1J7N contains two copies of the functional molecule (compare with the biological unit). Use the Hide.. tool in FirstGlance to simplify to one copy.
• Anthrax edema factor (2002) vs. edema factor complexed with calmodulin, (2002). Calmodulin activates the adenylyl cyclase exotoxin activity. Note that 1K93 contains three copies of the functional dimer (compare with the biological unit). Use the Hide.. tool in FirstGlance to simplify to one dimer. See also other calmodulin structures.
  
  Botulinum Neurotoxins, "BoTox®"
• Botulinum toxins, some of the most deadly toxins known, bind strongly and specifically to protein and ganglioside receptors localized to nerve cell membranes. Toxin molecules are thought to enter temporary openings in synaptic vesicles. As the vesicles are recycled, toxin gains access to the cytoplasm, where its light chain inactivates neuromuscular junctions, causing paralysis.
• Botulinum neurotoxin serotype B, carboxy-terminal domain of the heavy chain, complexed to the toxin-binding region of its protein receptor, the luminal portion of synaptotagmin II, residues 44-60 ( 2006). This portion of synamtotagmin II is intrinsically disordered, but forms an alpha helix by induced fit to the BoTox.
• Botulinum neurotoxin serotype A ("BoTox®") light chain, inactivated by two mutations, complexed to the carboxy terminal domain, residues 141-204, of human SNAP-25 ( 2004). SNAP-25 is a SNARE protein involved in neurotransmitter release. The light chain of botulinum toxin is a zinc metalloprotease that inactivates SNAREs at neuromuscular junctions, producing paralysis. This structure confirms that the protease uses exosites, remote from the catalytic site, to recognize its substrate.
• Botulinum neurotoxin serotype B complexed to sialyllactose ( 2000). Sialyllactose is a partial mimic of a ganglioside. Gangliosides and protein receptors on neurons are critical for toxin binding. This structure has the entire toxin molecule, including its catalytic, translocation, and binding domains.

CHALLENGING
• Collagen fiber, (1994). Here is an interactive tutorial about collagen.
  

• EF Hand binding calcium, animated: see Recoverin, which is a calcium-activated myristoyl switch involved in vision.
• Calmodulin:
  • With calcium, (1994).
  • With calcium and bound portion of myosin light chain kinase, (1992).
  • With calcium and bound portion of calcium-activated potassium channel, (2001). First instance of calmodulin binding three alpha helices, with the N vs. C ends of calmodulin contacting different bound domains. Be sure to explore the biological unit which is the complete tetramer structure.

  See (under other categories)

• Anthrax edema toxin bound to calmodulin, with calmodulin in a new, extended conformation.
• Recoverin

  CHALLENGING

• Calmodulin, with calcium, showing flexibility of interdomain linker, (1995).
• Calmodulin, with calcium, complexed to fragment of myosin light chain kinase, (1992).

STRAIGHTFORWARD
• 200-phospholipid hydrated bilayer theoretical models in
  conformations (Heller, Schaefer & Schulten, J. Phys. Chem. 97:8343, 1993; PDB files redistributed with permission). Phospholipids are palmitoyl linoleoyl phosphatidyl choline. Palmitic acid is a saturated fatty acid with 16 carbons; linoleic acid is doubly unsaturated with 18 carbons and two double bonds.
  Figure at right (© 1996) "Five Bakers Dancing".
  
  
  
• Lipid Bilayers and the Gramicidin Channel / Modelo de bicapa lipídica y canal de gramicidina.
• Visualizations of the gramicidin channel passing water through a lipid bilayer.

• Water: theoretical simulation of 10 water molecules assembling into a hydrogen-bonded network. Also models of water freezing, and larger assemblies of liquid water.
  

STRAIGHTFORWARD
• Potassium channel, (1998, 3.2 Å). This structure was the foundation for Roderick McKinnon receiving the 2003 Nobel Prize in Chemistry. See another version below under "CHALLENGING". See also the excellent overview at Molecule of the Month.
• Aquaporin, a water channel, (2001). This structure, initially solved at low resolution in 2000 by electron crystallography (1fqy) was part of the foundation for Peter Agre receiving the 2003 Nobel Prize in Chemistry. The functional form of aquaporin is a homo-tetramer, so be sure to view the biological unit. See also the excellent overview at Molecule of the Month.
• A homo-heptameric membrane pore, Staphlococcal alpha-hemolysin, (1996).
• Intramembrane protease of the rhomboid family, core catalytic domain of E. coli GlpG, (2006). A transmembrane protein itself, GlpG cleaves substrate transmembrane protein within the hydrophobic membrane lipid environment. The catalytic site includes Ser201, His254, and water.
• Bacteriorhodopsin, a light-driven ion pump, (1990 by electron diffraction, 1995 by X-ray, 1999). Has seven trans-membrane alpha helices with retinal and associated lipid. Note the buried water.
• Outer membrane iron transporter of E. coli, (2002).
   
                       

  CHALLENGING

• theoretical model (Crouzy, Woolf & Roux, Biophys. J. 67:1370, 1994; PDB file redistributed with permission).
  • Visualizations of the gramicidin channel passing water through a lipid bilayer.
• Potassium channel with four antibody Fab fragments bound (2001, 2.0 Å). The channel is a homotetramer, but only one channel subunit is present in the asymmetric unit. Be sure to view the biological unit to see the entire channel!
• Photosynthetic reaction center, purple bacterium, (reported 1984, deposited in the Protein Data Bank 1988). This is the first high-resolution trans-membrane structure obtained by X-ray crystallography, earning its authors the 1988 Nobel Prize in Chemistry. (Here is a link to their original 1984 paper, not linked to the PDB record.)
• Photosynthetic reaction center with bacteriochlorophyll a, ubiquinone and iron, (1994).
• Calcium pumping ATPase, with cytoplasmic and transmembrane domains, (2000, 2004). Another conformation, based upon cryo-electron microscopy, provides a model for the catalytic cycle, (2002).
   
  
• Porin, sucrose specific, Salmonella, water and sucrose in the pores, (1998).
• Mechanosensitive channel, gated, "large", MscL homolog from Mycobacterium tuberculosis, (1998, 2007). See an animation of this channel closing and opening.
• Mechanosensitive channel, voltage sensitive, E. coli MscS, (2002, 2007).
• Outer membrane protein A of E. coli (2000). Compare with showing flexibility, (2001).
• Chloride channel, (2002). Note that the functional molecule (biological unit) is a dimer, but the crystal asymmetric unit is a tetramer. Use the Hide.. tool in FirstGlance to simplify the view to one dimer.
• Succinate:quinone oxidoreductase (SQR), also the succinate dehydrogenase of the Krebs cycle, composed of four protein chains and five prosthetic groups, including a heme buried in the membrane, (2003). This structure "reveals that electrons are tranferred in a path more than 40 Å in length from the succinate oxidation site at the FAD, by way of the three iron sulfur clusters, to the ubiquinone binding site".

Recoverin 1iku...1jsa

CHALLENGING
• Recoverin, a calcium-activated myristoyl switch, (NMR ensembles, see Note #2) without calcium, myristate buried, (1995), and with calcium, myristate exposed, (1997).
  Brief introduction to recoverin and morphs of the transition.

  See also (under other categories)

• Calcineurin.

Genes were shown to reside in DNA in 1944 (Avery et al.) and this became widely accepted after the 1952 experiments of Hershey and Chase. The double helical structure of the DNA was predicted by James Watson and Francis Crick in 1953 (Nobel Prize, 1962). Their prediction was based in part upon X-ray diffraction studies by Rosalind Franklin, to whom Watson and Maurice Wilkins gave inadequate credit (see Rosalind Franklin: Dark Lady of DNA by Brenda Maddox, HarperCollins, 2002). The predicted B-form double helix was not confirmed with atomic-resolution crystal structures until 1973, first by using dinucleotides of RNA (Rosenberg et al.). The first crystal structure containing more than a full turn of the double helix was not solved until 1980 (Wing et al. 1981, 12 base pairs). The lag of more than a quarter century between prediction and empirical confirmation involved development of X-ray crystallography for macromolecules, and the need to produce a short, defined sequence of DNA for crystallization. This brief account is based upon a review by Berman, Gelbin, and Westbrook (Prog. Biophys. molec. Biol. 66:255, 1996), where the references will be found.

STRAIGHTFORWARD


• BUILD YOUR OWN DNA in B or A form, from a sequence that you specify, with optional energy minimization, at Model.It!
  
  
• DNA double helix (B form), 12 base pairs, one turn, (first full turn solved crystallographically, see above). This is an empirical crystallographic structure: notice the substantial and variable deviations from coplanarity for the base pairs. (1986) has almost the same sequence, but can you find the mismatched base pair? (See Brown et al.).
  See the interactive DNA molecule in English, en Espagñol, and other languages.

  

• DNA double helix (B form), 36 base pairs (3 full turns), ideal theoretical model,
• DNA double helix (A form), 36 base pairs, ideal theoretical model,
• DNA double helix, 12 base pairs,
• Interactive comparison of A, B, and Z forms of DNA.

• DNA double helix, two turns of chromatin theoretical model, 171 base pairs, This beautiful model from 1983 was constructed before the crystallographic structure of a nucleosome was reported in 1998: See also Nucleosomes.
• DNA/RNA hybrid double helix, (1995).
• Transfer RNA (Phe), (1974-1978). ( [2000] is a more challenging tRNA.)

  CHALLENGING

• DNA B form to Z form transition, (2005). The cover of the issue of Nature reporting this structure showed a theoretical model with longer B- and Z-form ends (shown at right), kindly provided for this Atlas by Kyeong Kyu Kim. View this model In order to solve this structure, the Z-DNA portion was stabilized by Z-DNA-binding proteins. The surprise is that base pairing is disrupted at only a single pair at the transition point. Sequences near promotors often favor Z-DNA, enabling them to trap negative supercoiling that occurs behind a moving polymerase, or during nucleosome unwrapping. Z-DNA cannot participate in a nucleosome, hence exposing it to transcription factors.
• Hammerhead ribozyme, (1994). The crystal asymmetric unit contains three copies of the biological unit, which has two RNA strands (A and B). Use the Hide.. tool in FirstGlance to simplify by hiding chains C, D, E and F.
• RNA self-splicing group I intron with both exons, (2004). While most introns are removed by a large ribonucleoprotein complex, the spliceosome, a subset catalyze their own excision without accessory factors. 1U6B is the first structure to include an active site (with magnesium) plus an intron and two exons, representing the splicing intermediate before the exon ligation step.

STRAIGHTFORWARD
• Lac repressor bound to specific DNA sequence, (2002). See also animations of nonspecific binding converting to specific binding and bending the DNA, as in the movie at right. Questions for students are provided.
• DNA polymerase complexed with DNA, (1996).
• Lambda repressor complexed to DNA, (1992).
• Zinc finger (Zif268) complexed to DNA, (1996).
• TATA-box binding protein, human, complexed to DNA, (1996).
• EcoRV endonuclease complexed to DNA, (1995).
• SarA transcriptional regulator of virulence factors in Staphylococcus aureus, (2001).
• HIN recombinase with specific contacts in both the major and minor grooves of the DNA double helix, (1994).
• Sliding clamp, processivity factor, a DNA encircling ring that serves as a docking site for DNA polymerases. (2010). (Also known as proliferating cell nuclear antigen. PCNA.)

  CHALLENGING

• RNA polymerase (T7 bacteriophage), with DNA template and nascent RNA, (1999).
• Recombinase (Flp) with enclosed Holliday junction of DNA, (2000).
• DNA mismatch repair protein MutS binding to a mismatch, (2000).
  • See if you can find the mismatch in the DNA double helix! To simplify the view, use Isolate.. in FirstGlance and check DNA.
  • Another case of MutS with bound DNA is (2000): what is wrong with the DNA there?
• Ku heterodimer bound to DNA, (2001). Facilitates repair of double-strand DNA breaks by non-homologous end-joining. Encircles the DNA double helix with a steric fit, avoiding base contacts.

  ENORMOUS

• Nucleosomes 
  • Nucleosome (DNA histone complex), (1997).
  • Tetranucleosome, (2006). The authors built a model of a chromatin fiber (not shown in this Atlas) in which the H4 tail can interact with H2A-H2B across an internucleosomal interface (as chemical crosslinking evidence suggests that it does).
  • Kaposi's sarcoma Herpesvirus protein bound to nucleosome, (2006). This virus protein (LANA) attaches viral genes (episomes) to mitotic chromosomes, ensuring faithful partitioning into progeny cells. This crystal structure shows that the LANA N-terminus (residues 1-23) binds to histones H2A-H2B in the same region thought to be occupied by the H4 tail in chromatin fibers. In fact, in these crystals, the H4 tail bound to some of the same regions through a crystal contact (not shown in this Atlas).
• Ribosomes 

  • Key: 3 tRNAs mRNA Large subunit (top): protein, RNA Small subunit (bottom): protein, RNA

    Here is an excellent interactive introduction to ribosome structure exploring a structure that includes 3 transfer RNAs and messenger RNA. Crystallographic ribosome structures were the basis for the 2009 Nobel Prize in Chemistry, and are among the highest impact structural discoveries of all time. The ribosome is the largest asymmetric structure solved by crystallography. Its enormous size makes it difficult to accommodate in FirstGlance.

Simplified model of SV40 capsid. Click on image for an interactive explanation.

Images of virions elsewhere:
• VIPERdb Virus Particle Explorer at The Scripps Research Institute.
• Virus World at the University of Wisconsin.

  CHALLENGING

• Simplified model of SV40 capsid: Each of the 360 chains has been reduced to a single "atom", and the enclosing icosahedron is represented.
  

  Cutaway view of the capsid of human hepatitis B virus.

• FirstGlance needs further development before it can show virus capsids. However, here is an interactive view of the capsid of human hepatitis B virus.

STRAIGHTFORWARD
• HIV protease with inhibitor, 2002).
• Animation of HIV protease binding inhibitor: see Enzymes.
• SARS coronavirus spike protein complexed to its receptor, angiotensin-converting enzyme 2 (ACE2), (2005). This crystal asymmetric unit contains 2 copies of the heterodimer biological unit. Use the Hide.. tool in FirstGlance to simplify by hiding one heterodimer.
  
  ENORMOUS
• See Kaposi's sarcoma protein bound to a nucleosome.

CHALLENGING

• The bacterial flagellar hook, model of a molecular universal joint.
  
  See also Bacterial Flagellar Structures at Atomic Resolution.
  
  
• Bacterial cell wall puncturing device of bacteriophage T4, also known as tail lysozyme, (2002). If you are familiar with protein structures, you will notice that the asymmetric unit is an impossible protein 3D structure. Be sure to look at the biological unit!

• Cutaway view showing the inside of a proteasome (1PMA).

  Proteasome (1995). From the archeon Thermoplasma acidophilum.
• HslU protease/HslV chaperone complex (2000). From Hemophilus influenzae.
• Chaperonin, GroEL-GroES (1997). From E. coli.

  SEE ALSO (under other categories)

• The Ribosome.
• The Nucleosome.

STRAIGHTFORWARD

    Antibody
• Complete IgG antibody, (1997).
  See interactive antibody tutorial at UMass in English, auf Deutsch.
• Complete IgG antibody with finger-like loop able to fit into the crevice in HIV gp120 that accomodates CD4, (2001). The finger-like loop is heavy chain CDR3, 18 residues numbered 94-101 (including inserted residues numbered 100A-100J). A synthetic peptide mimicking this CDR H3 neutralized HIV. To locate the loop, use Find.. in FirstGlance, and enter 94-101 and chain=h and *.ca.
• Fab fragment of antibody bound to lysozyme antigen, (1991).
  
      MHC
• Major histocompatibility complex (MHC), mouse class I, with viral peptide, (1992). To compare with a different viral peptide, see
• Major histocompatibility complex (MHC), mouse class II, with peptide from chicken lysozyme, (2000). The crystal asymmetric unit contains two copies of the hetero-trimer biological unit. Use the Hide.. tool in FirstGlance to simplify to one trimer.
• Major histocompatibility complex (MHC), human class II, with peptide from HIV Gag protein, (2004). T cell activation sometimes requires residues in the peptide that extend beyond the MHC groove. Here, a previously unknown peptide conformation is observed in which the carboxy terminus folds up and back, providing a required portion of the epitope. This could turn out to be a common situation. Also present in this complex is staphylococcal enterotoxin, which binds to the MHC and was used to promote crystallization.
• CD1b complexed to ganglioside GM2, (2002). CD1b is thought to present microbial lipids, including mycobacterial mycolates, to T lymphocytes, aiding in immune defenses against microbes. CD1's are structurally very similar to MHC proteins.
• CD1d complexed to alpha-galactosylceramide, (2005). This complex stimulates human and mouse natural killer T cells. Alpha-stereoisomers of glycosphingolipids, absent from mammals, are found in microbes and marine sponges. CD1's are structurally very similar to MHC proteins. The crystal asymmetric unit contains two copies of the heterodimer biological unit. Use the Hide.. tool in FirstGlance to simplify to one heterodimer.
  
      Cytokines
• Interleukin-1 receptor complexed to IL-1 receptor antagonist, human, expressed in E. coli, (1997).
• Interleukin-2 complexed to the Alpha, Beta, and Gamma chains of its receptor, (2006). The crystal asymmetric unit contains two copies of the hetero-tetramer biological unit. Use the Hide.. tool in FirstGlance to simplify to one heterotetramer.
• Interleukin-4 complexed to alpha-chain of receptor, human, expressed in E. coli, (1999).
• Interferon Gamma, bovine, expressed in E. coli, (2000).
• Chemokine IL-8, human (mutated), expressed in E. coli, (1997).
  
      Immuno-Receptors
• CTLA-4 bound to B7-1 (external domains only), (2001). The divalent homodimers of both molecules are believed to form chains in the immunological synapse (as shown in the image at right).
   
• Defensin (Rhesus theta defensin one, RTD-1), an antibacterial cyclic 18-amino acid peptide, (20-model NMR structure, see Note #2, 2001). Each half is coded by a different gene. Cyclization is thought to increase resistance to exoproteases (Trabi & Craik, TiBS 27:132). To see the cyclizing peptide bond in FirstGlance, use the Vines/Sticks view, and check More Detail.
  

  CHALLENGING

• CD4 (human) complexed to HIV gp120 and Fab (human), (2000).
• CD8 complexed to MHC class I, (1998). Only the terminal domains of the CD8 alpha-alpha homodimer are present. The MHC class I in this complex is mouse H-2Kb with vesicular stomatitis virus VSV8 peptide (same as 2VAA above). The crystal asymmetric unit contains two copies of the hetero-pentamer biological unit. Use the Hide.. tool in FirstGlance to simplify to one hetero-pentamer.
• T Cell Receptor (αβ), complexed to HTLV1 viral peptide presented by HLA-A2, (1996).
• T Cell Receptor (γδ), (2001). The crystal asymmetric unit contains four copies of the heterodimer biological unit. Use the Hide.. tool in FirstGlance to simplify to one heterodimer.

• Capsular polysaccharide, E. coli, (1977).
• Chondroitin-4-sulfate, sodium salt, (1978).
• Heparin (2-model NMR structure) (1993).
• Starch V-amylose, a single-helical poly-glucose with a central channel, When iodine stains starch blue, the iodine is included in the central channel (see ChemWiki at UCDavis).

• A deeply knotted protein chain, (2000). You won't be able to discern the knot by simple observation. See Knots in Proteins for an explanation and convincing visualizations.
• The cyclic cystine knot (CCK) motif involves penetration of a small ring, formed by two disulfide bonds and their connecting peptide backbone segments, by a third disulfide bond (Trabi & Craik, TiBS 27:132). Found in plant defense proteins called cyclotides, the first CCK structure reported was that of (10-model NMR structure, 1995).
• Intrinsically disordered chains that fit together in a stable heterodimer via "mutual synergistic folding". The heterodimer between p160 receptor coactivator and CBP/p300 transcriptional coactivator, (2002), is a member of a family of ligand-activated transcription factors involved in nuclear hormone receptors.
• Chaperone SicP maintaining Salmonella SptP virulence effector protein (105 residues) in a largely "unfolded" state, presumably to facilitate type III secretion, (2001).
• Lantibiotic mersacidin has non-standard amino acids involved in post-translational intra-chain cyclization via thioether bonds, (2000). To see the thioethers, Isolate one chain and use the Vines/Sticks view, checking More Detail. Then to see one more, depress the Ligands+ button, and check Smaller ligands. See also PNAS 101:11448, 2004.
• Naturally-occurring cyclic peptides.

Some proteins must remain disordered in order to perform their functions. Some disordered proteins achieve a stable fold only when they bind to a stably folded partner. By some esitmates, about 10% of all proteins are fully disordered, and about 40% of eukaryotic proteins have at least one long (>50 amino acids) disordered loop (Tompa, P., Trends Biochem. Sci. 27:527, 2002). See examples and prediction servers at Intrinsically Disordered Protein.


	At left is an animation of a heat shock/chaperonin protein fragment. Residues 1-70 are disordered; 71-109 are alpha helical. This animates 20 models from an NMR experiment, (2011). Charges are colored blue=positive and red=negative. A high charge density prevents folding. For comparison, at right is an animation of 20 NMR models of a protein of similar length that folds into a stable domain (2n5a). (2015). See Intrinsically Disordered Protein.
Animations will stop after 25 cycles. Shift+Re-load this page to restart the animations.



• To see all models at once for the disorderd protein consult Note 2.
• Human p27Kip1 kinase inhibitory domain (chain C, pink) is intrinsically disordered but forms a stable complex with the dimer of cyclin A/cyclin-dependent kinase 2 (chains A, B, blue and green):
• The N-terminal residues of the GCN4 DNA-binding domain are largely unstructured until they encounter DNA (Hollenbeck et al., Protein Sci. 11:2740, 2002). In complex with cognate DNA, they form a two helix leucine zipper, You will see only half of this structure until you visualize the biological unit.

Amyloids are deposits of fibrous, insoluble, aggregated misfolded protein. They are prominent in many diseases including Alzheimer's, Parkinson's, and Huntington's. Whether the amyloid deposits cause the disease, or are an after-effect, remains a subject of investigation. Because they are insoluble, it has been difficult to determine the structures of amyloids. Some structures have been determined by unusual methods such as solid-state NMR. An overview of what is known will be found in Molecule of the Month, and here is a more detailed 2015 review.


• Beta-amyloid fibril derived from Alzheimer's disease brain, (2013).
  
  
• Human prion protein (PrP) disease mutant Met129Val increases susceptibility to neurodegenerative disease. Here a crystal structure of a PrP segment containing the mustation suggests how amyloid fibers may form, (2010). View the biological unit to see a model of part of the insoluble fiber. The mutant peptide can be seen in (2010).
  

1. To find the experimental method:
   • In FirstGlance:

     Snapshot from FirstGlance in Jmol showing Method.

     • The method is given in the Molecule Information Tab (the first tab).
   • In Proteopedia:
     • If a resolution is given just below the molecule, the method is usually X-ray crystallography. To be sure, click on the link to RCSB ( under Resources).
     • If a number of "NMR models" is given, the method is usually solution nuclear magnetic resonance.
   
   
   

   Snapshot from FirstGlance in Jmol: View All NMR Models

2. To see an NMR ensemble of models:
   • FirstGlance shows you, initially, only the first model of the ensemble. If you opt to use Java, there is a link View All Models (in the Molecule Information Tab, which is the first tab).

     20 NMR models. Intrinsically Disordered.	21 NMR models. Stable Fold.

   
   
   

3. Snapshot from FirstGlance in Jmol: links to Biological Unit.

   To see the biological unit: View the structure in FirstGlance. Initially, FirstGlance shows you the asymmetric unit. This is often not the functional form of the molecule, which is called the "biological unit". You can click on the term Biological Unit in FirstGlance for an explanation of these terms. There you will find a link to view the biological unit.

• 2002, February: Created as part of the (now defunct) Protein Explorer project.
• 2008: Restructured to offer links to Proteopedia and FirstGlance in Jmol.
• 2012, September: Restructured to eliminate links and references to Protein Explorer.
• 2015, November: Minor updates.
• 2016, February: Major maintenance.
  • Released under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
  • Added several new entries.
  • Added a new detailed lesson plan.
  • Added a new section about intrinsically unstructured proteins.
  • Added a new section about Amyloids.
  • Fixed all broken links and removed links to defunct resources.
  • Temporarily removed links to alpha-carbon-only structures as FirstGlance could not handle these acceptably at the time.

Suggestions to Eric Martz.