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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.

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.

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The interface area of protein–protein complexes. Histogram of the values of the interface area B = ASA1 + ASA2 − ASA12 in 19 antigen–antibody complexes, 23 protease–inhibitor complexes and 33 other complexes. Interfaces with an area in the range 1200–2000 Å2 are labelled ‘standard size’. Adapted from Lo Conte et al. (1999 ▶).
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fig1: The interface area of protein–protein complexes. Histogram of the values of the interface area B = ASA1 + ASA2 − ASA12 in 19 antigen–antibody complexes, 23 protease–inhibitor complexes and 33 other complexes. Interfaces with an area in the range 1200–2000 Å2 are labelled ‘standard size’. Adapted from Lo Conte et al. (1999 ▶).

Mentions: The interaction of cognate antibodies with protein antigens plays an essential role in the immune system of vertebrates. It is a paradigm of specific recognition and one of the best represented in the PDB (Braden & Poljak, 2000 ▶; Sundberg & Mariuzza, 2002 ▶). Table 1 ▶ includes 18 protein antigen–antibody complexes and Fig. 1 ▶ shows the size distribution of their interfaces along with those of other transient complexes. The size is estimated as the interface area B = ASA1 + ASA2 − ASA12 calculated as the solvent-accessible surface area ASA12 of the complex less that of the dissociated components ASA1 and ASA2 (Lee & Richards, 1971 ▶; Chothia & Janin, 1975 ▶; note that other authors often report the quantity B/2). The antibody and the antigen moieties of the complex contribute almost equally to B. The distribution of the values is narrow for antigen–antibody complexes relative to the other types. All but one of the 19 interfaces are of ‘standard size’, with B in the range 1200–2000 Å2. The average interface atom loses about 10 Å2 of ASA in the complex and therefore a standard-size interface involves about 80 atoms belonging to approximately 23 amino-acid residues on each component.


Macromolecular recognition in the Protein Data Bank.

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

The interface area of protein–protein complexes. Histogram of the values of the interface area B = ASA1 + ASA2 − ASA12 in 19 antigen–antibody complexes, 23 protease–inhibitor complexes and 33 other complexes. Interfaces with an area in the range 1200–2000 Å2 are labelled ‘standard size’. Adapted from Lo Conte et al. (1999 ▶).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: The interface area of protein–protein complexes. Histogram of the values of the interface area B = ASA1 + ASA2 − ASA12 in 19 antigen–antibody complexes, 23 protease–inhibitor complexes and 33 other complexes. Interfaces with an area in the range 1200–2000 Å2 are labelled ‘standard size’. Adapted from Lo Conte et al. (1999 ▶).
Mentions: The interaction of cognate antibodies with protein antigens plays an essential role in the immune system of vertebrates. It is a paradigm of specific recognition and one of the best represented in the PDB (Braden & Poljak, 2000 ▶; Sundberg & Mariuzza, 2002 ▶). Table 1 ▶ includes 18 protein antigen–antibody complexes and Fig. 1 ▶ shows the size distribution of their interfaces along with those of other transient complexes. The size is estimated as the interface area B = ASA1 + ASA2 − ASA12 calculated as the solvent-accessible surface area ASA12 of the complex less that of the dissociated components ASA1 and ASA2 (Lee & Richards, 1971 ▶; Chothia & Janin, 1975 ▶; note that other authors often report the quantity B/2). The antibody and the antigen moieties of the complex contribute almost equally to B. The distribution of the values is narrow for antigen–antibody complexes relative to the other types. All but one of the 19 interfaces are of ‘standard size’, with B in the range 1200–2000 Å2. The average interface atom loses about 10 Å2 of ASA in the complex and therefore a standard-size interface involves about 80 atoms belonging to approximately 23 amino-acid residues on each component.

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