A Coarse-Grained Methodology Identifies Intrinsic Mechanisms That Dissociate Interacting Protein Pairs

Frontiers in Molecular Biosciences
Haleh AbdizadehCanan Atilgan

Abstract

We address the problem of triggering dissociation events between proteins that have formed a complex. We have collected a set of 25 non-redundant, functionally diverse protein complexes having high-resolution three-dimensional structures in both the unbound and bound forms. We unify elastic network models with perturbation response scanning (PRS) methodology as an efficient approach for predicting residues that have the propensity to trigger dissociation of an interacting protein pair, using the three-dimensional structures of the bound and unbound proteins as input. PRS reveals that while for a group of protein pairs, residues involved in the conformational shifts are confined to regions with large motions, there are others where they originate from parts of the protein unaffected structurally by binding. Strikingly, only a few of the complexes have interface residues responsible for dissociation. We find two main modes of response: In one mode, remote control of dissociation in which disruption of the electrostatic potential distribution along protein surfaces play the major role; in the alternative mode, mechanical control of dissociation by remote residues prevail. In the former, dissociation is triggered by changes in the ...Continue Reading

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Methods Mentioned

BETA
electron
x-ray scattering
X-ray
NMR

Software Mentioned

ZDOCK
STAMP
ENM
STRIDE
ANM
VMD
DEPTH
PRS
GNM
APBS

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