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5em9

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Crystal structure of the SNX27 PDZ domain bound to the phosphorylated C-terminal 5HT4(a)R PDZ binding motif

Structural highlights

5em9 is a 2 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SNX27_RAT Involved in endocytic trafficking (By similarity). In T lymphocytes, participates in endocytic recycling pathway. Recruits PSCDBP and HT4R to early endosomes (By similarity).

Publication Abstract from PubMed

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 beta2 adrenergic 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.

A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex.,Clairfeuille T, Mas C, Chan AS, Yang Z, Tello-Lafoz M, Chandra M, Widagdo J, Kerr MC, Paul B, Merida I, Teasdale RD, Pavlos NJ, Anggono V, Collins BM Nat Struct Mol Biol. 2016 Sep 5. doi: 10.1038/nsmb.3290. PMID:27595347^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Clairfeuille T, Mas C, Chan AS, Yang Z, Tello-Lafoz M, Chandra M, Widagdo J, Kerr MC, Paul B, Merida I, Teasdale RD, Pavlos NJ, Anggono V, Collins BM. A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. Nat Struct Mol Biol. 2016 Sep 5. doi: 10.1038/nsmb.3290. PMID:27595347 doi:http://dx.doi.org/10.1038/nsmb.3290