4p2a

Structure of mouse VPS26A bound to rat SNX27 PDZ domain

spinqualitylabelsall models 4p2a, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p2a is a 2 chain structure with sequence from Mus musculus 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 2.7Å Ligands: HG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function VP26A_MOUSE Essential component of the retromer complex, a complex required to retrieve lysosomal enzyme receptors (IGF2R and M6PR) from endosomes to the trans-Golgi network. Also required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Publication Abstract from PubMed 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 beta-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. A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer.,Gallon M, Clairfeuille T, Steinberg F, Mas C, Ghai R, Sessions RB, Teasdale RD, Collins BM, Cullen PJ Proc Natl Acad Sci U S A. 2014 Aug 18. pii: 201410552. PMID:25136126 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Sorting nexin 3D structures Vacuolar protein sorting-associated protein 3D structures

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