The Structural Basis of Peptide-Protein Binding Strategies

Nir London; Dana Movshovitz-Attias; Ora Schueler-Furman

doi:10.1016/j.str.2009.11.012

The Structural Basis of Peptide-Protein Binding Strategies

Nir London, Dana Movshovitz-Attias, Ora Schueler-Furman^*

^*Corresponding author for this work

Department of Microbiology and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

342 Scopus citations

Abstract

Peptide-protein interactions are very prevalent, mediating key processes such as signal transduction and protein trafficking. How can peptides overcome the entropic cost involved in switching from an unstructured, flexible peptide to a rigid, well-defined bound structure? A structure-based analysis of peptide-protein interactions unravels that most peptides do not induce conformational changes on their partner upon binding, thus minimizing the entropic cost of binding. Furthermore, peptides display interfaces that are better packed than protein-protein interfaces and contain significantly more hydrogen bonds, mainly those involving the peptide backbone. Additionally, "hot spot" residues contribute most of the binding energy. Finally, peptides tend to bind in the largest pockets available on the protein surface. Our study is based on peptiDB, a new and comprehensive data set of 103 high-resolution peptide-protein complex structures. In addition to improved understanding of peptide-protein interactions, our findings have direct implications for the structural modeling, design, and manipulation of these interactions.

Original language	English
Pages (from-to)	188-199
Number of pages	12
Journal	Structure
Volume	18
Issue number	2
DOIs	https://doi.org/10.1016/j.str.2009.11.012
State	Published - 10 Feb 2010

Bibliographical note

Funding Information:
We would like to thank Joe Dundas for assisting with the CASTp analysis, and William Sheffler for the creation and assistance with RosettaHoles. We thank Monika Fuxreiter for sharing with us the amino acid composition data. All structural images have been produced using PyMOL software ( DeLano, 2002 ). This work was supported by the Israel Science Foundation, founded by the Israel Academy of Science and Humanities (grant number 306/6), and the German-Israeli Foundation for Scientific Research and Development (Young Scientists Program 2159-1709.3/2006).

Keywords

PROTEINS

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10.1016/j.str.2009.11.012

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The Structural Basis of Peptide-Protein Binding Strategies

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