6gvc
From Proteopedia
Structure of ArhGAP12 bound to G-Actin
Structural highlights
Function[ACTS_RABIT] Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells. [RHG12_MOUSE] GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. Publication Abstract from PubMedRPEL proteins, which contain the G-actin-binding RPEL motif, coordinate cytoskeletal processes with actin dynamics. We show that the ArhGAP12- and ArhGAP32-family GTPase-activating proteins (GAPs) are RPEL proteins. We determine the structure of the ArhGAP12/G-actin complex, and show that G-actin contacts the RPEL motif and GAP domain sequences. G-actin inhibits ArhGAP12 GAP activity, and this requires the G-actin contacts identified in the structure. In B16 melanoma cells, ArhGAP12 suppresses basal Rac and Cdc42 activity, F-actin assembly, invadopodia formation and experimental metastasis. In this setting, ArhGAP12 mutants defective for G-actin binding exhibit more effective downregulation of Rac GTP loading following HGF stimulation and enhanced inhibition of Rac-dependent processes, including invadopodia formation. Potentiation or disruption of the G-actin/ArhGAP12 interaction, by treatment with the actin-binding drugs latrunculin B or cytochalasin D, has corresponding effects on Rac GTP loading. The interaction of G-actin with RPEL-family rhoGAPs thus provides a negative feedback loop that couples Rac activity to actin dynamics. RPEL-family rhoGAPs link Rac/Cdc42 GTP loading to G-actin availability.,Diring J, Mouilleron S, McDonald NQ, Treisman R Nat Cell Biol. 2019 Jul;21(7):845-855. doi: 10.1038/s41556-019-0337-y. Epub 2019 , Jun 17. PMID:31209295[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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