PDBsum entry 4p2a

Transport protein

PDB id: 4p2a

Contents

Protein chains

287 a.a.

97 a.a.

Metals

_HG ×2

Waters ×35

PDB id:

4p2a

Name:

Transport protein

Title:

Structure of mouse vps26a bound to rat snx27 pdz domain

Structure:

Vacuolar protein sorting-associated protein 26a. Chain: a. Synonym: h58 protein, h beta 58, vesicle protein sorting 26a, mvps26, vps26a. Engineered: yes. Sorting nexin-27. Chain: b. Synonym: map-responsive gene protein, methamphetamine-responsive transcript 1 protein, pdz-protein mrt1.

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Gene: vps26a, vps26. Expressed in: escherichia coli. Expression_system_taxid: 562. Rattus norvegicus. Rat. Organism_taxid: 10116.

Resolution:

2.70Å R-factor: 0.219 R-free: 0.259

Authors:

T.Clairfeuille,M.Gallon,C.Mas,R.Ghai,R.Teasdale,P.Cullen,B.Collins

Key ref:

M.Gallon et al. (2014). A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer. Proc Natl Acad Sci U S A, 111, E3604. PubMed id: 25136126 DOI: 10.1073/pnas.1410552111

Date:

03-Mar-14 Release date: 03-Sep-14

Protein chain

P40336  (VP26A_MOUSE) -  Vacuolar protein sorting-associated protein 26A from Mus musculus

Seq: 327 a.a.

Struc: 287 a.a.

Protein chain

Q8K4V4  (SNX27_RAT) -  Sorting nexin-27 from Rattus norvegicus

Seq: 539 a.a.

Struc: 97 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1073/pnas.1410552111

Proc Natl Acad Sci U S A 111:E3604 (2014)

PubMed id: 25136126

A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer.

M.Gallon, T.Clairfeuille, F.Steinberg, C.Mas, R.Ghai, R.B.Sessions, R.D.Teasdale, B.M.Collins, P.J.Cullen.

ABSTRACT

The sorting nexin 27 (SNX27)-retromer complex is a major regulator of endosome-to-plasma membrane recycling of transmembrane cargos that contain a PSD95, Dlg1, zo-1 (PDZ)-binding motif. Here we describe the core interaction in SNX27-retromer assembly and its functional relevance for cargo sorting. Crystal structures and NMR experiments reveal that an exposed β-hairpin in the SNX27 PDZ domain engages a groove in the arrestin-like structure of the vacuolar protein sorting 26A (VPS26A) retromer subunit. The structure establishes how the SNX27 PDZ domain simultaneously binds PDZ-binding motifs and retromer-associated VPS26. Importantly, VPS26A binding increases the affinity of the SNX27 PDZ domain for PDZ- binding motifs by an order of magnitude, revealing cooperativity in cargo selection. With disruption of SNX27 and retromer function linked to synaptic dysfunction and neurodegenerative disease, our work provides the first step, to our knowledge, in the molecular description of this important sorting complex, and more broadly describes a unique interaction between a PDZ domain and an arrestin-like fold.