Abstract
BackgroundIn a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding.ResultsIn this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%). This proportion is even greater in the interface regions (41%). Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins.ConclusionOur study provides qualitative information about induced fit. These results could be of help for flexible docking.
Highlights
In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding
We propose an investigation of structural changes in protein complexes, from a local point-of-view, via a structural alphabet developed in our lab
We study the preference for particular letters in the interface regions, and analyze the structural letter substitutions that occur at the interfaces
Summary
In a number of protein-protein complexes, the 3D structures of bound and unbound partners significantly differ, supporting the induced fit hypothesis for protein-protein binding. Most of biochemical reactions inherent to the life of a cell are mediated by protein-protein interactions, e. Interfaces between interacting proteins have been extensively studied for decades [3,4]. It has been shown that they have distinct features when compared to non-specific interfaces observed in protein crystals [5,6,7,8,9], or when compared to the rest of the protein surface [10,11,12,13,14,15,16]. Different models have been proposed for the protein binding process. The first was the 'lock and (page number not for citation purposes)
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