RGD Reference Report - A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer. - Rat Genome Database

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

Authors: Gallon, Matthew  Clairfeuille, Thomas  Steinberg, Florian  Mas, Caroline  Ghai, Rajesh  Sessions, Richard B  Teasdale, Rohan D  Collins, Brett M  Cullen, Peter J 
Citation: Gallon M, etal., Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3604-13. doi: 10.1073/pnas.1410552111. Epub 2014 Aug 18.
RGD ID: 13508597
Pubmed: (View Article at PubMed) PMID:25136126
DOI: Full-text: DOI:10.1073/pnas.1410552111

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 ß-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.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Snx27  (sorting nexin 27)


Additional Information