6bbq
Model for extended volume of truncated monomeric Cytohesin-3 (Grp1; amino acids 63-399) E161A Arf6 Q67L fusion protein
Structural highlights
FunctionARF6_HUMAN GTP-binding protein involved in protein trafficking; regulates endocytic recycling and cytoskeleton remodeling. May modulate vesicle budding and uncoating within the Golgi apparatus. Functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in the regulation of dendritic spine development (By similarity). Contributes to the regulation of dendritic branching and filopodia extension.[1] [2] [3] CYH3_MOUSE Promotes guanine-nucleotide exchange on ARF1. Promotes the activation of ARF factors through replacement of GDP with GTP.[4] Publication Abstract from PubMedMembrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and a membrane-targeting module such as a pleckstrin homology (PH) domain. The catalytic output of cytohesin family Arf GEFs is controlled by autoinhibitory interactions that impede accessibility of the exchange site in the Sec7 domain. These restraints can be relieved through activator Arf-GTP binding to an allosteric site comprising the PH domain and proximal autoinhibitory elements (Sec7-PH linker and C-terminal helix). Small-angle X-ray scattering and negative-stain electron microscopy were used to investigate the structural organization and conformational dynamics of cytohesin-3 (Grp1) in autoinhibited and active states. The results support a model in which hinge dynamics in the autoinhibited state expose the activator site for Arf-GTP binding, while subsequent C-terminal helix unlatching and repositioning unleash conformational entropy in the Sec7-PH linker to drive exposure of the exchange site. Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors.,Malaby AW, Das S, Chakravarthy S, Irving TC, Bilsel O, Lambright DG Structure. 2018 Jan 2;26(1):106-117.e6. doi: 10.1016/j.str.2017.11.019. Epub 2017, Dec 21. PMID:29276036[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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