2fau

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Crystal structure of human vps26

Structural highlights

2fau is a 1 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 2.1Å
Ligands:CAF, GOL
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VP26A_HUMAN Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins (Probable). The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R (PubMed:15078902, PubMed:15078903). Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15247922). Required for the endosomal localization of FAM21A (indicative for the WASH complex) (PubMed:22070227). Required for the endosomal localization of TBC1D5 (PubMed:20923837). Mediates retromer cargo reognition of SORL1 and is involved in trafficking of SORL1 implicated in sorting and processing of APP (PubMed:22279231). Involved in retromer-independent lysosomal sorting of F2R (PubMed:16407403). Involved in recycling of ADRB2 (PubMed:21602791). Enhances the affinity of SNX27 for PDZ-binding motifs in cargo proteins (By similarity).[UniProtKB:P40336][1] [2] [3] [4] [5] [6] [7] [8] [9] [10]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The mammalian retromer complex consists of SNX1, SNX2, Vps26, Vps29 and Vps35, and retrieves lysosomal enzyme receptors from endosomes to the trans-Golgi network. The structure of human Vps26A at 2.1-A resolution reveals two curved beta-sandwich domains connected by a polar core and a flexible linker. Vps26 has an unpredicted structural relationship to arrestins. The Vps35-binding site on Vps26 maps to a mobile loop spanning residues 235-246, near the tip of the C-terminal domain. The loop is phylogenetically conserved and provides a mechanism for Vps26 integration into the complex that leaves the rest of the structure free for engagements with membranes and for conformational changes. Hydrophobic residues and a glycine in this loop are required for integration into the retromer complex and endosomal localization of human Vps26, and for the function of yeast Vps26 in carboxypeptidase Y sorting.

The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain.,Shi H, Rojas R, Bonifacino JS, Hurley JH Nat Struct Mol Biol. 2006 Jun;13(6):540-8. Epub 2006 May 28. PMID:16732284[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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See Also

References

  1. ↑ Seaman MN. Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. J Cell Biol. 2004 Apr;165(1):111-22. PMID:15078902 doi:http://dx.doi.org/10.1083/jcb.200312034
  2. ↑ Arighi CN, Hartnell LM, Aguilar RC, Haft CR, Bonifacino JS. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor. J Cell Biol. 2004 Apr;165(1):123-33. PMID:15078903 doi:http://dx.doi.org/10.1083/jcb.200312055
  3. ↑ Verges M, Luton F, Gruber C, Tiemann F, Reinders LG, Huang L, Burlingame AL, Haft CR, Mostov KE. The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor. Nat Cell Biol. 2004 Aug;6(8):763-9. Epub 2004 Jul 11. PMID:15247922 doi:10.1038/ncb1153
  4. ↑ Gullapalli A, Wolfe BL, Griffin CT, Magnuson T, Trejo J. An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins. Mol Biol Cell. 2006 Mar;17(3):1228-38. Epub 2006 Jan 11. PMID:16407403 doi:http://dx.doi.org/10.1091/mbc.E05-09-0899
  5. ↑ Harbour ME, Breusegem SY, Seaman MN. Recruitment of the endosomal WASH complex is mediated by the extended 'tail' of Fam21 binding to the retromer protein Vps35. Biochem J. 2012 Feb 15;442(1):209-20. doi: 10.1042/BJ20111761. PMID:22070227 doi:http://dx.doi.org/10.1042/BJ20111761
  6. ↑ Fjorback AW, Seaman M, Gustafsen C, Mehmedbasic A, Gokool S, Wu C, Militz D, Schmidt V, Madsen P, Nyengaard JR, Willnow TE, Christensen EI, Mobley WB, Nykjaer A, Andersen OM. Retromer binds the FANSHY sorting motif in SorLA to regulate amyloid precursor protein sorting and processing. J Neurosci. 2012 Jan 25;32(4):1467-80. doi: 10.1523/JNEUROSCI.2272-11.2012. PMID:22279231 doi:http://dx.doi.org/10.1523/JNEUROSCI.2272-11.2012
  7. ↑ Harbour ME, Breusegem SY, Antrobus R, Freeman C, Reid E, Seaman MN. The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics. J Cell Sci. 2010 Nov 1;123(Pt 21):3703-17. doi: 10.1242/jcs.071472. Epub 2010 Oct, 5. PMID:20923837 doi:http://dx.doi.org/10.1242/jcs.071472
  8. ↑ Temkin P, Lauffer B, Jager S, Cimermancic P, Krogan NJ, von Zastrow M. SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. Nat Cell Biol. 2011 Jun;13(6):715-21. doi: 10.1038/ncb2252. Epub 2011 May 22. PMID:21602791 doi:http://dx.doi.org/10.1038/ncb2252
  9. ↑ Harterink M, Port F, Lorenowicz MJ, McGough IJ, Silhankova M, Betist MC, van Weering JR, van Heesbeen RG, Middelkoop TC, Basler K, Cullen PJ, Korswagen HC. A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion. Nat Cell Biol. 2011 Jul 3;13(8):914-23. doi: 10.1038/ncb2281. PMID:21725319 doi:http://dx.doi.org/10.1038/ncb2281
  10. ↑ Steinberg F, Gallon M, Winfield M, Thomas EC, Bell AJ, Heesom KJ, Tavare JM, Cullen PJ. A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport. Nat Cell Biol. 2013 May;15(5):461-71. doi: 10.1038/ncb2721. Epub 2013 Apr 7. PMID:23563491 doi:http://dx.doi.org/10.1038/ncb2721
  11. ↑ Shi H, Rojas R, Bonifacino JS, Hurley JH. The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain. Nat Struct Mol Biol. 2006 Jun;13(6):540-8. Epub 2006 May 28. PMID:16732284 doi:10.1038/nsmb1103

Contents


PDB ID 2fau

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