Interaction of nonstructural protein 5A of the hepatitis C virus with Src homology 3 domains using noncanonical binding sites.
Src homology 3 (SH3) domains are widely known for their ability to interact with other proteins using the canonical PxxP binding motif. Besides those well-characterized interaction modes, there is an increasing number of SH3 domain-containing complexes that lack this motif. Here we characterize the interaction of SH3 domains, in particular the Bin1-SH3 domain, with the intrinsically disordered part of nonstructural protein 5A of the hepatitis C virus using noncanonical binding sites in addition to its PxxP motif. These binding regions partially overlap with regions that have previously been identified as having an increased propensity to form α-helices. Remarkably, upon interaction with the Bin1-SH3 domain, the α-helical propensity decreases and a fuzzy complex is formed.
Institut de Biologie Structurale, Université Grenoble 1 , 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
Melanie
M
Schwarten
Zsófia
Z
Sólyom
Sophie
S
Feuerstein
Amine
A
Aladağ
Silke
S
Hoffmann
Dieter
D
Willbold
Bernhard
B
Brutscher
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001665:Binding Sites; D016174:Hepacivirus / Q000378:metabolism; D008958:Models, Molecular; D017361:Viral Nonstructural Proteins / Q000737:chemistry* / Q000378:metabolism; D018909:src Homology Domains / Q000502:physiology*; D012324:RNA-Dependent RNA Polymerase
D048868:Adaptor Proteins, Signal Transducing; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase