6U3E

Best fitting antiparallel model for Volume 1 of truncated dimeric Cytohesin-3 (Grp1; amino acids 14-399)

Summary for 6U3E

• Entry DOI: 10.2210/pdb6u3e/pdb
• EMDB information: 20628 20629
• Descriptor: Cytohesin-3, INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE (2 entities in total)
• Functional Keywords: arf gef, phosphoinositide binding, sec7 domain, ph domain, endocytosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 94003.68

Authors

Das, S.,Lambright, D.G. (deposition date: 2019-08-21, release date: 2019-09-25, Last modification date: 2023-11-29)

Primary citation

Das, S.,Malaby, A.W.,Nawrotek, A.,Zhang, W.,Zeghouf, M.,Maslen, S.,Skehel, M.,Chakravarthy, S.,Irving, T.C.,Bilsel, O.,Cherfils, J.,Lambright, D.G.
Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes.
Structure, 27:1782-, 2019

PubMed Abstract: Membrane dynamic processes require Arf GTPase activation by guanine nucleotide exchange factors (GEFs) with a Sec7 domain. Cytohesin family Arf GEFs function in signaling and cell migration through Arf GTPase activation on the plasma membrane and endosomes. In this study, the structural organization of two cytohesins (Grp1 and ARNO) was investigated in solution by size exclusion-small angle X-ray scattering and negative stain-electron microscopy and on membranes by dynamic light scattering, hydrogen-deuterium exchange-mass spectrometry and guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange assays. The results suggest that cytohesins form elongated dimers with a central coiled coil and membrane-binding pleckstrin-homology (PH) domains at opposite ends. The dimers display significant conformational heterogeneity, with a preference for compact to intermediate conformations. Phosphoinositide-dependent membrane recruitment is mediated by one PH domain at a time and alters the conformational dynamics to prime allosteric activation by Arf-GTP. A structural model for membrane targeting and allosteric activation of full-length cytohesin dimers is discussed.

PubMed: 31601460
DOI: 10.1016/j.str.2019.09.007

Experimental method

ELECTRON MICROSCOPY (53 Å)