Abstract
SummaryProtein interactions are often accompanied by significant changes in conformation. We have analyzed the relationships between protein structures and the conformational changes they undergo upon binding. Based upon this, we introduce a simple measure, the relative solvent accessible surface area, which can be used to predict the magnitude of binding-induced conformational changes from the structures of either monomeric proteins or bound subunits. Applying this to a large set of protein complexes suggests that large conformational changes upon binding are common. In addition, we observe considerable enrichment of intrinsically disordered sequences in proteins predicted to undergo large conformational changes. Finally, we demonstrate that the relative solvent accessible surface area of monomeric proteins can be used as a simple proxy for protein flexibility. This reveals a powerful connection between the flexibility of unbound proteins and their binding-induced conformational changes, consistent with the conformational selection model of molecular recognition.
Highlights
Interactions between polypeptide chains are integral to most biological processes
Protein interactions can be accompanied by substantial disorder-to-order transitions in the case of intrinsically disordered proteins (IDPs), which are disordered in isolation but which can often be induced to fold in the presence of binding partners (Wright and Dyson, 2009)
While interface size shows some correlation with conformational change, the solvent accessible surface area of a bound subunit relative to the value expected for a monomeric protein of its size is a much better predictor
Summary
Protein interactions are often accompanied by significant changes in conformation. We have analyzed the relationships between protein structures and the conformational changes they undergo upon binding. We introduce a simple measure, the relative solvent accessible surface area, which can be used to predict the magnitude of binding-induced conformational changes from the structures of either monomeric proteins or bound subunits. Applying this to a large set of protein complexes suggests that large conformational changes upon binding are common. We demonstrate that the relative solvent accessible surface area of monomeric proteins can be used as a simple proxy for protein flexibility This reveals a powerful connection between the flexibility of unbound proteins and their binding-induced conformational changes, consistent with the conformational selection model of molecular recognition
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