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6vac

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Revision as of 07:20, 15 April 2020

Mouse retromer (VPS26/VPS35/VPS29) heterotrimer

6vac, resolution 5.70Å

Structural highlights

6vac is a 3 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Vps35, Mem3 (LK3 transgenic mice), Vps26a, Vps26 (LK3 transgenic mice), Vps29 (LK3 transgenic mice)
Experimental data:	Check to display Experimental Data
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[VPS35_MOUSE] 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 CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. 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 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. 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 and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for endosomal localization of WASHC2 and mediates the association of the CSC with the WASH complex (By similarity).[UniProtKB:Q96QK1] [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). [VP26A_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).

Publication Abstract from PubMed

Metazoan retromer (VPS26/VPS35/VPS29) associates with sorting nexins on endosomal tubules to sort proteins to the trans-Golgi network or plasma membrane. Mechanisms of metazoan retromer assembly remain undefined. We combine single-particle cryoelectron microscopy with biophysical methods to uncover multiple oligomer structures. 2D class averages reveal mammalian heterotrimers; dimers of trimers; tetramers of trimers; and flat chains. These species are further supported by biophysical solution studies. We provide reconstructions of all species, including key sub-structures ( approximately 5 A resolution). Local resolution variation suggests that heterotrimers and dimers adopt multiple conformations. Our structures identify a flexible, highly conserved electrostatic dimeric interface formed by VPS35 subunits. We generate structure-based mutants to disrupt this interface in vitro. Equivalent mutations in yeast demonstrate a mild cargo-sorting defect. Our data suggest the metazoan retromer is an adaptable and plastic scaffold that accommodates interactions with different sorting nexins to sort multiple cargoes from endosomes their final destinations.

Mammalian Retromer Is an Adaptable Scaffold for Cargo Sorting from Endosomes.,Kendall AK, Xie B, Xu P, Wang J, Burcham R, Frazier MN, Binshtein E, Wei H, Graham TR, Nakagawa T, Jackson LP Structure. 2020 Feb 4. pii: S0969-2126(20)30009-5. doi:, 10.1016/j.str.2020.01.009. PMID:32027819^[1]

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

References

↑ Kendall AK, Xie B, Xu P, Wang J, Burcham R, Frazier MN, Binshtein E, Wei H, Graham TR, Nakagawa T, Jackson LP. Mammalian Retromer Is an Adaptable Scaffold for Cargo Sorting from Endosomes. Structure. 2020 Feb 4. pii: S0969-2126(20)30009-5. doi:, 10.1016/j.str.2020.01.009. PMID:32027819 doi:http://dx.doi.org/10.1016/j.str.2020.01.009

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6vac"

@@ Line 3: / Line 3: @@
 <SX load='6vac' size='340' side='right' viewer='molstar' caption='[[6vac]], [[Resolution|resolution]] 5.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6vac]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VAC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VAC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6vac]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VAC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VAC FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vac OCA], [http://pdbe.org/6vac PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vac RCSB], [http://www.ebi.ac.uk/pdbsum/6vac PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vac ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Vps35, Mem3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Vps26a, Vps26 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Vps29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vac FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vac OCA], [http://pdbe.org/6vac PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vac RCSB], [http://www.ebi.ac.uk/pdbsum/6vac PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vac ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 25: / Line 26: @@
 </SX>
 [[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Jackson, L P]]
 [[Category: Kendall, A K]]

6vac

From Proteopedia

Revision as of 07:20, 15 April 2020

Mouse retromer (VPS26/VPS35/VPS29) heterotrimer

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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