PDBsum entry 4cz2

Signaling protein

PDB id: 4cz2

Contents

Protein chains

172 a.a.

168 a.a.

Ligands

GCP ×3

Metals

_MG ×3

Waters ×113

PDB id:

4cz2

Name:

Signaling protein

Title:

Complex of human varp-ankrd1 with rab32-gppcp. Selenomet derivative.

Structure:

Ras-related protein rab-32. Chain: a, b, c. Fragment: residues 450-640. Synonym: rab32. Engineered: yes. Ankyrin repeat domain-containing protein 27. Chain: d, e, f. Fragment: first ankyrin repeat-containing domain, residues 1-225. Synonym: vps9 domain-containing protein, vps9-domain ankyrin repeat

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: rosetta 2.

Resolution:

2.97Å R-factor: 0.197 R-free: 0.232

Authors:

I.Perez-Dorado,I.B.Schaefer,A.J.Mccoy,D.J.Owen,P.R.Evans

Key ref:

G.G.Hesketh et al. (2014). VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface. Dev Cell, 29, 591-606. PubMed id: 24856514 DOI: 10.1016/j.devcel.2014.04.010

Date:

16-Apr-14 Release date: 04-Jun-14

Protein chains

Q13637  (RAB32_HUMAN) -  Ras-related protein Rab-32 from Homo sapiens

Seq: 225 a.a.

Struc: 172 a.a.*

Protein chains

Q96NW4  (ANR27_HUMAN) -  Ankyrin repeat domain-containing protein 27 from Homo sapiens

Seq: 1050 a.a.

Struc: 168 a.a.

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

DOI no: 10.1016/j.devcel.2014.04.010

Dev Cell 29:591-606 (2014)

PubMed id: 24856514

VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface.

G.G.Hesketh, I.Pérez-Dorado, L.P.Jackson, L.Wartosch, I.B.Schäfer, S.R.Gray, A.J.McCoy, O.B.Zeldin, E.F.Garman, M.E.Harbour, P.R.Evans, M.N.Seaman, J.P.Luzio, D.J.Owen.

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.