Abstract
Members of the Rho family of small G proteins transduce signals from plasma-membrane receptors and control cell adhesion, motility and shape by actin cytoskeleton formation1–4. They also activate other kinase cascades. Like all other GTPases, Rho proteins act as molecular switches, with an active GTP-bound form and an inactive GDP-bound form5. The active conformation is promoted by guanine-nucleotide exchange factors, and the inactive state by GTPase-activating proteins (GAPs) which stimulate the intrinsic GTPase activity of small G proteins6. Rho-specific GAP domains are found in a wide variety of large, multi-functional proteins7. Here we report the crystal structure of an active 242-residue C-terminal fragment of human p50rhoGAP8. The structure is an unusual arrangement of nine α-helices, the core of which includes a four-helix bundle. Residues conserved across the rhoGAP family are largely confined to one face of this bundle, which may be an interaction site for target G proteins. In particular, we propose that Arg 85 and Asn 194 are involved in binding G proteins and enhancing GTPase activity.
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Barrett, T., Xiao, B., Dodson, E. et al. The structure of the GTPase-activating domain from p50rhoGAP. Nature 385, 458–461 (1997). https://doi.org/10.1038/385458a0
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DOI: https://doi.org/10.1038/385458a0
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