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TitleStructural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors.
Journal, issue, pagesStructure, Vol. 26, Issue 1, Page 106-117.e6, Year 2018
Publish dateJan 2, 2018
AuthorsAndrew W Malaby / Sanchaita Das / Srinivas Chakravarthy / Thomas C Irving / Osman Bilsel / David G Lambright /
PubMed AbstractMembrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and ...Membrane 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.
External linksStructure / PubMed:29276036 / PubMed Central
MethodsEM (single particle)
Resolution35.0 Å
Structure data

7077

6bbp

EMDB-7077, PDB-6bbp:
Model for compact volume of truncated monomeric Cytohesin-3 (Grp1; amino acids 63-399) E161A 6GS Arf6 Q67L fusion protein
Method: EM (single particle) / Resolution: 35.0 Å

7078

6bbq

EMDB-7078, PDB-6bbq:
Model for extended volume of truncated monomeric Cytohesin-3 (Grp1; amino acids 63-399) E161A Arf6 Q67L fusion protein
Method: EM (single particle) / Resolution: 35.0 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM / Guanosine triphosphate

ChemComp-MG:
Unknown entry

ChemComp-4IP:
INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE

Source
  • mus musculus (house mouse)
  • homo sapiens (human)
KeywordsLIPID BINDING PROTEIN / Guanine nucleotide exchange factor / Arf GTPase / Fusion protein / Inositol 1 / 3 / 4 / 5-tetrakisphosphate

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