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The identification of protein domains that mediate functional interactions between Rab-GTPases and RabGAPs using 3D protein modeling

Authors Davie JJ, Faitar SL

Received 1 September 2016

Accepted for publication 23 November 2016

Published 10 April 2017 Volume 2017:10 Pages 47—56


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Juan Fernandez-Recio

Jeremiah J Davie, Silviu L Faitar

Department of Biology and Mathematics, School of Arts, Sciences, and Education, D’Youville College, Buffalo, NY, USA

Currently, time-consuming serial in vitro experimentation involving immunocytochemistry or radiolabeled materials is required to identify which of the numerous Rab-GTPases (Rab) and Rab-GTPase activating proteins (RabGAP) are capable of functional interactions. These interactions are essential for numerous cellular functions, and in silico methods of reducing in vitro trial and error would accelerate the pace of research in cell biology. We have utilized a combination of three-dimensional protein modeling and protein bioinformatics to identify domains present in Rab proteins that are predictive of their functional interaction with a specific RabGAP. The RabF2 and RabSF1 domains appear to play functional roles in mediating the interaction between Rabs and RabGAPs. Moreover, the RabSF1 domain can be used to make in silico predictions of functional Rab/RabGAP pairs. This method is expected to be a broadly applicable tool for predicting protein–protein interactions where existing crystal structures for homologs of the proteins of interest are available.

GTP hydrolysis, Rab proteins, RabGAPs, protein–protein interactions, structural informatics, computational biology, Evi5, Evi5L

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