ARHGAP15: Human Rho GTPase Activating Protein 15
PDB Code: 3BYI
GTPases are essential components within numerous cellular pathways and the Rho members of this family are responsible in the control of signaling pathways linking membrane receptors to the assembly and disassembly of adhesion complexes and actin cytoskeletal dynamics and gene regulation through down stream effectors. Owing to its wide range of cellular functions, fine regulation of the signaling process is highly necessary, which is achieved through a specific group of proteins termed RhoGAPs or ARHGAPs. GTPase activating proteins (GAPs) are encoded by approximately 0.5 % of the total genes encoded in human and function through directly interacting with GTP bound active GTPase in the transition state and accelerate the hydrolysis up to 105 times. ARHGAP15 have been reported to function as a GAP for Rac1 GTPase but the physiological role of the GAP still remains unknown.
We have determined the structure of ARHGAP15, which is completely alpha helical. Its structure is similar to other RhoGAP members containing four bundled helices, with a conserved arginine residue that participates directly in catalysis by providing the ‘arginine finger’ residue. This residue protrudes into the GTPase active site and positions the catalytically vital Gln 61 residue in the switch II region during transition state, accelerating the catalytic cycle.
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