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Crystal structure of mouse Vps29 complexed with Mn2+
Structural highlights
FunctionVPS29_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). 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 PubMedThe retromer complex is responsible for the retrieval of mannose 6-phosphate receptors from the endosomal system to the Golgi. Here we present the crystal structure of the mammalian retromer subunit mVps29 and show that it has structural similarity to divalent metal-containing phosphoesterases. mVps29 can coordinate metals in a similar manner but has no detectable phosphoesterase activity in vitro, suggesting a unique specificity or function. The mVps29 and mVps26 subunits bind independently to mVps35 and together form a high-affinity heterotrimeric subcomplex. Mutagenesis reveals the structural basis for the interaction of mVps29 with mVps35 and subsequent association with endosomal membranes in vivo. A conserved hydrophobic surface distinct from the primary Vps35p binding site mediates assembly of the Vps29p-Vps26p-Vps35p subcomplex with sorting nexins in yeast, and mutation of either site results in a defect in retromer-dependent membrane trafficking. Vps29 has a phosphoesterase fold that acts as a protein interaction scaffold for retromer assembly.,Collins BM, Skinner CF, Watson PJ, Seaman MN, Owen DJ Nat Struct Mol Biol. 2005 Jul;12(7):594-602. Epub 2005 Jun 19. PMID:15965486[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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