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Computational identification of novel peripheral protein‐membrane interactions
Author(s) -
Kufareva Irina,
Dancea Felician,
Kiran Mahadev Ravi,
Polonskaya Zinaida,
Overduin Michael,
Abagyan Ruben
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.811.5
Subject(s) - membrane , peripheral membrane protein , membrane protein , chemistry , biophysics , membrane curvature , lipid bilayer , homology modeling , bilayer , biochemistry , integral membrane protein , biology , enzyme
Soluble proteins are recruited to membranes in many cellular processes. The information about the ability of a protein to transiently interact with the bilayer often helps understanding its function. However, obtaining such information experimentally is costly and complicated. In this study, we present a fast computational method for detecting potential peripheral membrane proteins and their individual membrane‐inserting residues. The method relies on 3D structure alone and does not refer to homology with known membrane‐targeting modules. It is based on the analysis of protein surface curvature and statistical membrane propensities of the chemical groups. Using the method, we screened a set of 521 medium‐size protein domains with known X‐ray structures and residue chemical shift assignments. We identified four novel transient membrane binders: plant acetyltransferase AT1G, bacterial methionine sulfoxide reductase, human ARF‐1, and human von Willebrand factor. Bilayer interaction of these proteins was assessed by monitoring chemical shift changes in their 1 H, 15 N HSQC spectra upon micelle addition. Based on the obtained per‐residue data, membrane docking position of each domain was determined by rigid‐body Monte Carlo optimization in a membrane/solvent boundary map. Analysis of the obtained positions proved the validity of our prediction. This work was supported by NIH grant 5‐R01‐GM071872‐02.