1XXM

The modular architecture of protein-protein binding site

Summary for 1XXM

• Entry DOI: 10.2210/pdb1xxm/pdb
• Related: 1S0W
• Descriptor: Beta-lactamase TEM, Beta-lactamase inhibitory protein, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: protein-protein complex; tem-1 beta-lactamase; beta-2 lactamase inhibitor protein; blip, israel structural proteomics center, ispc, structural genomics, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Escherichia coli; More
• Cellular location: Secreted: P35804
• Total number of polymer chains: 4
• Total formula weight: 92352.34

Authors

Reichmann, D.,Rahat, O.,Albeck, S.,Meged, R.,Dym, O.,Schreiber, G.,Israel Structural Proteomics Center (ISPC) (deposition date: 2004-11-07, release date: 2005-01-18, Last modification date: 2024-11-13)

Primary citation

Reichmann, D.,Rahat, O.,Albeck, S.,Meged, R.,Dym, O.,Schreiber, G.
The modular architecture of protein-protein binding interfaces
Proc.Natl.Acad.Sci.USA, 102:57-62, 2005

PubMed Abstract: Protein-protein interactions are essential for life. Yet, our understanding of the general principles governing binding is not complete. In the present study, we show that the interface between proteins is built in a modular fashion; each module is comprised of a number of closely interacting residues, with few interactions between the modules. The boundaries between modules are defined by clustering the contact map of the interface. We show that mutations in one module do not affect residues located in a neighboring module. As a result, the structural and energetic consequences of the deletion of entire modules are surprisingly small. To the contrary, within their module, mutations cause complex energetic and structural consequences. Experimentally, this phenomenon is shown on the interaction between TEM1-beta-lactamase and beta-lactamase inhibitor protein (BLIP) by using multiple-mutant analysis and x-ray crystallography. Replacing an entire module of five interface residues with Ala created a large cavity in the interface, with no effect on the detailed structure of the remaining interface. The modular architecture of binding sites, which resembles human engineering design, greatly simplifies the design of new protein interactions and provides a feasible view of how these interactions evolved.

PubMed: 15618400
DOI: 10.1073/pnas.0407280102

Experimental method

X-RAY DIFFRACTION (1.9 Å)