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Macromolecular recognition in the Protein Data Bank.

Janin J, Rodier F, Chakrabarti P, Bahadur RP - Acta Crystallogr. D Biol. Crystallogr. (2006)

Bottom Line: The geometric and physical chemical properties of the macromolecular interfaces that may govern the stability and specificity of recognition are explored in complexes and homodimers compared with crystal-packing interactions.Results of the CAPRI (critical assessment of predicted interactions) blind prediction experiment show that docking algorithms efficiently and accurately predict the mode of assembly of proteins that do not change conformation when they associate.They perform less well in the presence of large conformation changes and the experiment stimulates the development of novel procedures that can handle such changes.

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Affiliation: Laboratoire d'Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette, France. joel.janin@ibbmc.u-psud.fr

ABSTRACT
Crystal structures deposited in the Protein Data Bank illustrate the diversity of biological macromolecular recognition: transient interactions in protein-protein and protein-DNA complexes and permanent assemblies in homodimeric proteins. The geometric and physical chemical properties of the macromolecular interfaces that may govern the stability and specificity of recognition are explored in complexes and homodimers compared with crystal-packing interactions. It is found that crystal-packing interfaces are usually much smaller; they bury fewer atoms and are less tightly packed than in specific assemblies. Standard-size interfaces burying 1200-2000 A2 of protein surface occur in protease-inhibitor and antigen-antibody complexes that assemble with little or no conformation changes. Short-lived electron-transfer complexes have small interfaces; the larger size of the interfaces observed in complexes involved in signal transduction and homodimers correlates with the presence of conformation changes, often implicated in biological function. Results of the CAPRI (critical assessment of predicted interactions) blind prediction experiment show that docking algorithms efficiently and accurately predict the mode of assembly of proteins that do not change conformation when they associate. They perform less well in the presence of large conformation changes and the experiment stimulates the development of novel procedures that can handle such changes.

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The size of crystal-packing interfaces. Distribution of the interface area B of 1320 pairs of molecules in crystals of monomeric proteins analyzed by Janin & Rodier (1995 ▶). The average is B = 570 Å2. Interfaces with values of B comparable to those found in protein–protein complexes (B > 800 Å2) occur mostly in crystals with twofold symmetry; they form ‘crystal dimers’ that may be mistaken for real homodimers. In crystals with no twofold symmetry, the number of packing interfaces with B > 800 Å2 follows an extreme value distribution, approximated here by the red line (Janin, 1997 ▶). The boxed region includes 103 crystal dimers and 85 other large crystal-packing interfaces whose properties may be compared with those of the interfaces in complexes and homodimers (Bahadur et al., 2004 ▶).
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fig4: The size of crystal-packing interfaces. Distribution of the interface area B of 1320 pairs of molecules in crystals of monomeric proteins analyzed by Janin & Rodier (1995 ▶). The average is B = 570 Å2. Interfaces with values of B comparable to those found in protein–protein complexes (B > 800 Å2) occur mostly in crystals with twofold symmetry; they form ‘crystal dimers’ that may be mistaken for real homodimers. In crystals with no twofold symmetry, the number of packing interfaces with B > 800 Å2 follows an extreme value distribution, approximated here by the red line (Janin, 1997 ▶). The boxed region includes 103 crystal dimers and 85 other large crystal-packing interfaces whose properties may be compared with those of the interfaces in complexes and homodimers (Bahadur et al., 2004 ▶).

Mentions: From a structural point of view, there is an obvious difference between the two types of interfaces. The pairwise contacts in a protein crystal are much less extensive than in homodimers or complexes (Janin & Rodier, 1995 ▶; Dasgupta et al., 1997 ▶; Janin, 1997 ▶; Carugo & Argos, 1997 ▶). The average area of crystal-packing interfaces is only 570 Å2 per interface (Fig. 4 ▶), yet the total buried surface is large because each protein molecule makes 6–12 such interfaces (Janin & Rodier, 1995 ▶). Moreover, with few exceptions, proteins maintain the same structure to within 1 Å r.m.s.d. for the main chain in different crystal forms, suggesting that crystal packing has little effect on conformation.


Macromolecular recognition in the Protein Data Bank.

Janin J, Rodier F, Chakrabarti P, Bahadur RP - Acta Crystallogr. D Biol. Crystallogr. (2006)

The size of crystal-packing interfaces. Distribution of the interface area B of 1320 pairs of molecules in crystals of monomeric proteins analyzed by Janin & Rodier (1995 ▶). The average is B = 570 Å2. Interfaces with values of B comparable to those found in protein–protein complexes (B > 800 Å2) occur mostly in crystals with twofold symmetry; they form ‘crystal dimers’ that may be mistaken for real homodimers. In crystals with no twofold symmetry, the number of packing interfaces with B > 800 Å2 follows an extreme value distribution, approximated here by the red line (Janin, 1997 ▶). The boxed region includes 103 crystal dimers and 85 other large crystal-packing interfaces whose properties may be compared with those of the interfaces in complexes and homodimers (Bahadur et al., 2004 ▶).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2483476&req=5

fig4: The size of crystal-packing interfaces. Distribution of the interface area B of 1320 pairs of molecules in crystals of monomeric proteins analyzed by Janin & Rodier (1995 ▶). The average is B = 570 Å2. Interfaces with values of B comparable to those found in protein–protein complexes (B > 800 Å2) occur mostly in crystals with twofold symmetry; they form ‘crystal dimers’ that may be mistaken for real homodimers. In crystals with no twofold symmetry, the number of packing interfaces with B > 800 Å2 follows an extreme value distribution, approximated here by the red line (Janin, 1997 ▶). The boxed region includes 103 crystal dimers and 85 other large crystal-packing interfaces whose properties may be compared with those of the interfaces in complexes and homodimers (Bahadur et al., 2004 ▶).
Mentions: From a structural point of view, there is an obvious difference between the two types of interfaces. The pairwise contacts in a protein crystal are much less extensive than in homodimers or complexes (Janin & Rodier, 1995 ▶; Dasgupta et al., 1997 ▶; Janin, 1997 ▶; Carugo & Argos, 1997 ▶). The average area of crystal-packing interfaces is only 570 Å2 per interface (Fig. 4 ▶), yet the total buried surface is large because each protein molecule makes 6–12 such interfaces (Janin & Rodier, 1995 ▶). Moreover, with few exceptions, proteins maintain the same structure to within 1 Å r.m.s.d. for the main chain in different crystal forms, suggesting that crystal packing has little effect on conformation.

Bottom Line: The geometric and physical chemical properties of the macromolecular interfaces that may govern the stability and specificity of recognition are explored in complexes and homodimers compared with crystal-packing interactions.Results of the CAPRI (critical assessment of predicted interactions) blind prediction experiment show that docking algorithms efficiently and accurately predict the mode of assembly of proteins that do not change conformation when they associate.They perform less well in the presence of large conformation changes and the experiment stimulates the development of novel procedures that can handle such changes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratoire d'Enzymologie et de Biochimie Structurales, UPR9063, CNRS, 91198 Gif-sur-Yvette, France. joel.janin@ibbmc.u-psud.fr

ABSTRACT
Crystal structures deposited in the Protein Data Bank illustrate the diversity of biological macromolecular recognition: transient interactions in protein-protein and protein-DNA complexes and permanent assemblies in homodimeric proteins. The geometric and physical chemical properties of the macromolecular interfaces that may govern the stability and specificity of recognition are explored in complexes and homodimers compared with crystal-packing interactions. It is found that crystal-packing interfaces are usually much smaller; they bury fewer atoms and are less tightly packed than in specific assemblies. Standard-size interfaces burying 1200-2000 A2 of protein surface occur in protease-inhibitor and antigen-antibody complexes that assemble with little or no conformation changes. Short-lived electron-transfer complexes have small interfaces; the larger size of the interfaces observed in complexes involved in signal transduction and homodimers correlates with the presence of conformation changes, often implicated in biological function. Results of the CAPRI (critical assessment of predicted interactions) blind prediction experiment show that docking algorithms efficiently and accurately predict the mode of assembly of proteins that do not change conformation when they associate. They perform less well in the presence of large conformation changes and the experiment stimulates the development of novel procedures that can handle such changes.

Show MeSH
Related in: MedlinePlus