View source for 8ttc


==Structure of retromer VPS29-VPS35 (483-796) complexed with Fam21A repeat 20 (1289-1302)==
<StructureSection load='8ttc' size='340' side='right'caption='[[8ttc]], [[Resolution|resolution]] 3.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8ttc]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8TTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8TTC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.01&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8ttc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ttc OCA], [https://pdbe.org/8ttc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ttc RCSB], [https://www.ebi.ac.uk/pdbsum/8ttc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ttc ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VPS29_MOUSE VPS29_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). Has low protein phosphatase activity towards a serine-phosphorylated peptide derived from IGF2R (in vitro) (By similarity). Has no activity towards p-nitrophenylphosphate, p-nitrophenylphosphorylcholine or phosphatidylinositlphosphates (in vitro).
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== 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<ref>PMID:39116126</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 8ttc" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Chen K-E]]
[[Category: Collins BM]]
[[Category: Guo Q]]