PMID- 25136126 OWN - NLM STAT- MEDLINE DCOM- 20141112 LR - 20220309 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 111 IP - 35 DP - 2014 Sep 2 TI - A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer. PG - E3604-13 LID - 10.1073/pnas.1410552111 [doi] AB - 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. FAU - Gallon, Matthew AU - Gallon M AD - The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom; FAU - Clairfeuille, Thomas AU - Clairfeuille T AD - Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia; and. FAU - Steinberg, Florian AU - Steinberg F AD - The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom; FAU - Mas, Caroline AU - Mas C AD - Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia; and. FAU - Ghai, Rajesh AU - Ghai R AD - Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia; and. FAU - Sessions, Richard B AU - Sessions RB AD - School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom. FAU - Teasdale, Rohan D AU - Teasdale RD AD - Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia; and. FAU - Collins, Brett M AU - Collins BM AD - Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia; and b.collins@imb.uq.edu.au pete.cullen@bristol.ac.uk. FAU - Cullen, Peter J AU - Cullen PJ AD - The Henry Wellcome Integrated Signalling Laboratories, School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom; b.collins@imb.uq.edu.au pete.cullen@bristol.ac.uk. LA - eng SI - PDB/4P2A GR - MR/K018299/1/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140818 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Arrestin) RN - 0 (Nerve Tissue Proteins) RN - 0 (Protein Sorting Signals) RN - 0 (RNA, Small Interfering) RN - 0 (SNX27 protein, human) RN - 0 (Snx27 protein, mouse) RN - 0 (Snx27 protein, rat) RN - 0 (Sorting Nexins) RN - 0 (VPS26A protein, human) RN - 0 (Vesicular Transport Proteins) RN - 0 (Vps26 protein, mouse) SB - IM MH - Amino Acid Sequence MH - Animals MH - Arrestin/chemistry/genetics MH - Brain Diseases/genetics/metabolism/pathology MH - Crystallography, X-Ray MH - Endocytosis/*physiology MH - Endosomes/metabolism MH - HEK293 Cells MH - Humans MH - Mice MH - Molecular Sequence Data MH - Mutagenesis MH - Nerve Tissue Proteins/chemistry/genetics/metabolism MH - PDZ Domains/*genetics MH - Protein Folding MH - Protein Sorting Signals/genetics MH - RNA, Small Interfering/genetics MH - Rats MH - Sequence Homology, Amino Acid MH - Sorting Nexins/*chemistry/genetics/metabolism MH - Vesicular Transport Proteins/*chemistry/genetics/metabolism PMC - PMC4156734 OTO - NOTNLM OT - Alzheimer's disease OT - Down syndrome OT - Parkinson disease OT - endosomal recycling COIS- The authors declare no conflict of interest. EDAT- 2014/08/20 06:00 MHDA- 2014/11/13 06:00 PMCR- 2015/03/02 CRDT- 2014/08/20 06:00 PHST- 2014/08/20 06:00 [entrez] PHST- 2014/08/20 06:00 [pubmed] PHST- 2014/11/13 06:00 [medline] PHST- 2015/03/02 00:00 [pmc-release] AID - 1410552111 [pii] AID - 201410552 [pii] AID - 10.1073/pnas.1410552111 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2014 Sep 2;111(35):E3604-13. doi: 10.1073/pnas.1410552111. Epub 2014 Aug 18.