PDBsum entry 5em9

Protein transport

PDB id: 5em9

Contents

Protein chain

96 a.a.

Ligands

SEP-LEU-GLU-SER-CYS-PHE

Waters ×109

PDB id:

5em9

Name:

Protein transport

Title:

Crystal structure of the snx27 pdz domain bound to the phosphorylated c-terminal 5ht4(a)r pdz binding motif

Structure:

Sorting nexin-27. Chain: a. Fragment: pdz domain (unp residues 39-133). Synonym: map-responsive gene protein,methamphetamine-responsive transcript 1 protein,pdz-protein mrt1. Engineered: yes. Sep-leu-glu-ser-cys-phe. Chain: b. Engineered: yes

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: snx27, mrt1. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Homo sapiens. Human.

Resolution:

1.60Å R-factor: 0.170 R-free: 0.198

Authors:

B.M.Collins,T.Clairfeuille

Key ref:

T.Clairfeuille et al. (2016). A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. Nat Struct Mol Biol, 23, 921-932. PubMed id: 27595347

Date:

06-Nov-15 Release date: 07-Sep-16

Protein chain

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

Seq: 539 a.a.

Struc: 96 a.a.*

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

Nat Struct Mol Biol 23:921-932 (2016)

PubMed id: 27595347

A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex.

T.Clairfeuille, C.Mas, A.S.Chan, Z.Yang, M.Tello-Lafoz, M.Chandra, J.Widagdo, M.C.Kerr, B.Paul, I.Mérida, R.D.Teasdale, N.J.Pavlos, V.Anggono, B.M.Collins.

ABSTRACT

Recycling of internalized receptors from endosomal compartments is essential for the receptors' cell-surface homeostasis. Sorting nexin 27 (SNX27) cooperates with the retromer complex in the recycling of proteins containing type I PSD95-Dlg-ZO1 (PDZ)-binding motifs. Here we define specific acidic amino acid sequences upstream of the PDZ-binding motif required for high-affinity engagement of the human SNX27 PDZ domain. However, a subset of SNX27 ligands, such as the β₂adrenergic receptor and N-methyl-D-aspartate (NMDA) receptor, lack these sequence determinants. Instead, we identified conserved sites of phosphorylation that substitute for acidic residues and dramatically enhance SNX27 interactions. This newly identified mechanism suggests a likely regulatory switch for PDZ interaction and protein transport by the SNX27-retromer complex. Defining this SNX27 binding code allowed us to classify more than 400 potential SNX27 ligands with broad functional implications in signal transduction, neuronal plasticity and metabolite transport.