8ttu

Structure of SNX27 FERM complexed with Fam21A repeat 19 (1261 - 1274)

spinqualitylabelsall models 8ttu, resolution 2.36Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ttu is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.36Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SNX27_HUMAN 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 Endosomal membrane trafficking is mediated by specific protein coats and formation of actin-rich membrane domains. The Retromer complex coordinates with sorting nexin (SNX) cargo adaptors including SNX27, and the SNX27-Retromer assembly interacts with the Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex which nucleates actin filaments establishing the endosomal recycling domain. Crystal structures, modeling, biochemical, and cellular validation reveal how the FAM21 subunit of WASH interacts with both Retromer and SNX27. FAM21 binds the FERM domain of SNX27 using acidic-Asp-Leu-Phe (aDLF) motifs similar to those found in the SNX1 and SNX2 subunits of the ESCPE-1 complex. Overlapping FAM21 repeats and a specific Pro-Leu containing motif bind three distinct sites on Retromer involving both the VPS35 and VPS29 subunits. Mutation of the major VPS35-binding site does not prevent cargo recycling; however, it partially reduces endosomal WASH association indicating that a network of redundant interactions promote endosomal activity of the WASH complex. These studies establish the molecular basis for how SNX27-Retromer is coupled to the WASH complex via overlapping and multiplexed motif-based interactions required for the dynamic assembly of endosomal membrane recycling domains. Structural basis for coupling of the WASH subunit FAM21 with the endosomal SNX27-Retromer complex.,Guo Q, Chen KE, Gimenez-Andres M, Jellett AP, Gao Y, Simonetti B, Liu M, Danson CM, Heesom KJ, Cullen PJ, Collins BM Proc Natl Acad Sci U S A. 2024 Aug 13;121(33):e2405041121. doi: , 10.1073/pnas.2405041121. Epub 2024 Aug 8. PMID:39116126 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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