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PDBsum entry 5irc
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Protein binding
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PDB id
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5irc
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References listed in PDB file
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Key reference
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Title
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Deciphering the molecular and functional basis of rhogap family proteins: a systematic approach toward selective inactivation of rho family proteins.
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Authors
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E.Amin,
M.Jaiswal,
U.Derewenda,
K.Reis,
K.Nouri,
K.T.Koessmeier,
P.Aspenström,
A.V.Somlyo,
R.Dvorsky,
M.R.Ahmadian.
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Ref.
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J Biol Chem, 2016,
291,
20353-20371.
[DOI no: ]
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PubMed id
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Abstract
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RHO GTPase-activating proteins (RHOGAPs) are one of the major classes of
regulators of the RHO-related protein family that are crucial in many cellular
processes, motility, contractility, growth, differentiation, and development.
Using database searches, we extracted 66 distinct human RHOGAPs, from which 57
have a common catalytic domain capable of terminating RHO protein signaling by
stimulating the slow intrinsic GTP hydrolysis (GTPase) reaction. The specificity
of the majority of the members of RHOGAP family is largely uncharacterized.
Here, we comprehensively investigated the sequence-structure-function
relationship between RHOGAPs and RHO proteins by combining our in vitro data
with in silico data. The activity of 14 representatives of the RHOGAP family
toward 12 RHO family proteins was determined in real time. We identified and
structurally verified hot spots in the interface between RHOGAPs and RHO
proteins as critical determinants for binding and catalysis. We have found that
the RHOGAP domain itself is nonselective and in some cases rather inefficient
under cell-free conditions. Thus, we propose that other domains of RHOGAPs
confer substrate specificity and fine-tune their catalytic efficiency in cells.
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