Bottom - Index of papers - Paper in HTML - Abstract - RostGroup
| Title: | Protein-protein interaction hot spots carved into sequences |
| Author: | Yanay Ofran & Burkhard Rost |
| Quote: | PLoS Computationl Biology, 2007, 3:e119 |
Protein-protein interactions, a key to almost any biological process, are mediated by molecular mechanisms that are not entirely clear. The study of these mechanisms often focuses on all residues at protein-protein interfaces. However, only a small subset of all interface residues are actually essential for recognition or binding. Commonly referred to as "hot spots", these essential residues are defined as residues that impede protein-protein interactions if mutated. While no in silico tool identifies hot spots in unbound chains, numerous prediction methods were designed to identify all the residues in a protein that are likely to be a part of protein-protein interfaces. These methods typically identify successfully only a small fraction of all interface residues. Here, we analyzed the hypothesis that the two subsets correspond, i.e. that in silico methods may predict few residues because they preferentially predict hot spots. We demonstrate that this is indeed the case and that we can therefore predict directly from the sequence of a single protein which residues are interaction hot spots (without knowledge of the interaction partner). Our results suggested that most protein complexes are stabilized by similar basic principles. The ability to accurately and efficiently identify hot spots from sequence enables the annotation and analysis of protein-protein interaction hot spots in entire organisms and thus may benefit function prediction and drug development.
Availability: http://www.rostlab.org/services/isis
Synopsis (non technical summary)
Interactions between proteins underlie all biological processes. Hence, to fully understand or to control biological processes we need to unravel the principles of protein interactions. The quest for these principles has focused predominantly on the entire interfaces between two interacting proteins. However, it has been shown that only few of the interface residues are essential for the recognition and binding to other proteins. The identification of these residues, commonly referred to as binding "hot spots", is a first step toward understanding the function of proteins and studying their interactions. Experimentally, hot spots could be identified by mutating single residues - an expensive and laborious procedure which is not applicable on a large scale. Here, we show that it is possible to identify protein interaction hot spots computationally on a large scale based on the amino acid sequence of a single protein, without requiring the knowledge of its interaction partner. Our results suggest that most protein complexes are stabilized by similar basic principles. The ability to accurately and efficiently identify hot spots from sequence enables the annotation and analysis of protein-protein interaction hot spots in entire organism and thus may benefit function prediction and drug development.
Top -
Index of papers -
Paper in HTML -
Abstract -
RostGroup