Adding structural information to the von Hippel-Lindau (VHL) tumor suppressor interaction network.
The von Hippel-Lindau (VHL) tumor suppressor gene is a protein interaction hub, controlling numerous genes implicated in tumor progression. Here we focus on structural aspects of protein interactions for a list of 35 experimentally verified protein VHL (pVHL) interactors. Using structural information and computational analysis we have located three distinct interaction interfaces (A, B, and C). Interface B is the most versatile, recognizing a refined linear motif present in 17 otherwise non-related proteins. It has been possible to distinguish compatible and exclusive interactions by relating pVHL function to interaction interfaces and subcellular localization. A novel hypothesis is presented regarding the possible function of the N-terminus as an inhibitor of pVHL function.
Leonardi
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Department of Biology, University of Padua, 35131 Padua, Italy.
Murgia
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Tosatto
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human