4CYM

Complex of human VARP-ANKRD1 with Rab32-GppCp

Summary for 4CYM

• Entry DOI: 10.2210/pdb4cym/pdb
• Related: 4CZ2
• Descriptor: RAS-RELATED PROTEIN RAB-32, ANKYRIN REPEAT DOMAIN-CONTAINING PROTEIN 27, PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER, ... (5 entities in total)
• Functional Keywords: transport protein, varp, rab-effector, rab, endosome, vesicle trafficking, melanosome biogenesis
• Biological source: HOMO SAPIENS (HUMAN); More
• Cellular location: Mitochondrion: Q13637; Cytoplasm: Q96NW4
• Total number of polymer chains: 6
• Total formula weight: 144850.24

Authors

Perez-Dorado, I.,Schaefer, I.B.,McCoy, A.J.,Owen, D.J.,Evans, P.R. (deposition date: 2014-04-13, release date: 2014-06-04, Last modification date: 2023-12-20)

Primary citation

Hesketh, G.G.,Perez-Dorado, I.,Jackson, L.P.,Wartosch, L.,Schefer, I.B.,Gray, S.R.,Mccoy, A.J.,Zeldin, O.B.,Garman, E.F.,Harbour, M.E.,Evans, P.R.,Seaman, M.N.,Luzio, J.P.,Owen, D.J.
Varp is Recruited on to Endosomes by Direct Interaction with Retromer, Where Together They Function in Export to the Cell Surface.
Dev.Cell, 29:591-, 2014

PubMed Abstract: VARP is a Rab32/38 effector that also binds to the endosomal/lysosomal R-SNARE VAMP7. VARP binding regulates VAMP7 participation in SNARE complex formation and can therefore influence VAMP7-mediated membrane fusion events. Mutant versions of VARP that cannot bind Rab32:GTP, designed on the basis of the VARP ankyrin repeat/Rab32:GTP complex structure described here, unexpectedly retain endosomal localization, showing that VARP recruitment is not dependent on Rab32 binding. We show that recruitment of VARP to the endosomal membrane is mediated by its direct interaction with VPS29, a subunit of the retromer complex, which is involved in trafficking from endosomes to the TGN and the cell surface. Transport of GLUT1 from endosomes to the cell surface requires VARP, VPS29, and VAMP7 and depends on the direct interaction between VPS29 and VARP. Finally, we propose that endocytic cycling of VAMP7 depends on its interaction with VARP and, consequently, also on retromer.

PubMed: 24856514
DOI: 10.1016/J.DEVCEL.2014.04.010

Experimental method

X-RAY DIFFRACTION (2.8 Å)