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A Superfamily Reunion: Conserved Water Analysis of Small GTPases Using the Crystallography Tool DRoP
Author(s) -
Marcus Kendra,
Mattos Carla
Publication year - 2015
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.29.1_supplement.893.13
Subject(s) - gtpase , subfamily , rab , ras superfamily , biology , gtp' , effector , small gtpase , microbiology and biotechnology , protein family , conserved sequence , biochemistry , signal transduction , computational biology , peptide sequence , enzyme , gene
The Ras superfamily of GTPases is a family of monomeric molecular switches that regulate a variety of cellular processes, such as proliferation, migration, trafficking and vesicle formation. Subfamily classification includes Ras, Rho, Ran, Rab, and Arf/Sar. While the core structure of each small GTPase is conserved, each subfamily interacts with unique effectors that contribute to differing pathway regulation in the cell. The GTP/GDP cycle is a common regulatory feature of signaling output across GTPases. The GTP‐bound protein results in an active signaling cascade of interactions in the cell, and the hydrolysis of GTP to GDP turns off the signal. The current research focuses on how water‐mediated H‐bonding networks differ between the subfamily members with particular attention to their ability to promote intrinsic hydrolysis and communication between distant areas of the GTPases. Structural water molecules contribute to protein‐target specificity, enzyme catalysis, and protein dynamics. Detection of Related Solvent Positions (DRoP) is a computational tool that identifies conserved water molecules across multiple Protein Data Bank files. DRoP is employed to study conserved waters in each small GTPase subfamily classification. Several subfamily specific structural water patterns are seen through this analysis, in addition to highly conserved waters belonging to the entire superfamily. The discovery of both unique and common water networks between subfamilies aid in understanding functional differences between small GTPases. This work is funded by the National Science Foundation (NSF MCB‐1244203).