2r17

From Proteopedia

(Difference between revisions)

Current revision

Functional architecture of the retromer cargo-recognition complex

Structural highlights

2r17 is a 4 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 2.8Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VPS29_HUMAN 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).^[1]

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 retromer complex is required for the sorting of acid hydrolases to lysosomes, transcytosis of the polymeric immunoglobulin receptor, Wnt gradient formation, iron transporter recycling and processing of the amyloid precursor protein. Human retromer consists of two smaller complexes: the cargo recognition VPS26-VPS29-VPS35 heterotrimer and a membrane-targeting heterodimer or homodimer of SNX1 and/or SNX2 (ref. 13). Here we report the crystal structure of a VPS29-VPS35 subcomplex showing how the metallophosphoesterase-fold subunit VPS29 (refs 14, 15) acts as a scaffold for the carboxy-terminal half of VPS35. VPS35 forms a horseshoe-shaped, right-handed, alpha-helical solenoid, the concave face of which completely covers the metal-binding site of VPS29, whereas the convex face exposes a series of hydrophobic interhelical grooves. Electron microscopy shows that the intact VPS26-VPS29-VPS35 complex is a stick-shaped, flexible structure, approximately 21 nm long. A hybrid structural model derived from crystal structures, electron microscopy, interaction studies and bioinformatics shows that the alpha-solenoid fold extends the full length of VPS35, and that VPS26 is bound at the opposite end from VPS29. This extended structure presents multiple binding sites for the SNX complex and receptor cargo, and appears capable of flexing to conform to curved vesicular membranes.

Functional architecture of the retromer cargo-recognition complex.,Hierro A, Rojas AL, Rojas R, Murthy N, Effantin G, Kajava AV, Steven AC, Bonifacino JS, Hurley JH Nature. 2007 Oct 25;449(7165):1063-7. Epub 2007 Sep 23. PMID:17891154^[2]

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

References

↑ 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
↑ Hierro A, Rojas AL, Rojas R, Murthy N, Effantin G, Kajava AV, Steven AC, Bonifacino JS, Hurley JH. Functional architecture of the retromer cargo-recognition complex. Nature. 2007 Oct 25;449(7165):1063-7. Epub 2007 Sep 23. PMID:17891154 doi:10.1038/nature06216

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2r17"

@@ Line 3: / Line 3: @@
 <StructureSection load='2r17' size='340' side='right'caption='[[2r17]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2r17]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R17 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2r17]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2R17 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R17 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">VPS29 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VPS35, MEM3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2r17 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r17 OCA], [https://pdbe.org/2r17 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r17 RCSB], [https://www.ebi.ac.uk/pdbsum/2r17 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r17 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[https://www.uniprot.org/uniprot/VPS35_HUMAN VPS35_HUMAN]] Defects in VPS35 are the cause of Parkinson disease type 17 (PARK17) [MIM:[https://omim.org/entry/614203 614203]]. PARK17 is an autosomal dominant, adult-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain.<ref>PMID:21763482</ref> <ref>PMID:21763483</ref> <ref>PMID:22517097</ref>
 == Function ==
-[[https://www.uniprot.org/uniprot/VPS29_HUMAN VPS29_HUMAN]] 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).<ref>PMID:15247922</ref>  [[https://www.uniprot.org/uniprot/VPS35_HUMAN VPS35_HUMAN]] 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).<ref>PMID:15247922</ref>
+[https://www.uniprot.org/uniprot/VPS29_HUMAN VPS29_HUMAN] 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).<ref>PMID:15247922</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 18: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r1/2r17_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 39: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bonifacino, J S]]
+[[Category: Bonifacino JS]]
-[[Category: Effantin, G]]
+[[Category: Effantin G]]
-[[Category: Hierro, A]]
+[[Category: Hierro A]]
-[[Category: Hurley, J H]]
+[[Category: Hurley JH]]
-[[Category: Kajava, A V]]
+[[Category: Kajava AV]]
-[[Category: Murthy, N]]
+[[Category: Murthy N]]
-[[Category: Rojas, A L]]
+[[Category: Rojas AL]]
-[[Category: Rojas, R]]
+[[Category: Rojas R]]
-[[Category: Steven, A C]]
+[[Category: Steven AC]]
-[[Category: Membrane]]
-[[Category: Phosphorylation]]
-[[Category: Protein transport]]

2r17

From Proteopedia

Current revision

Functional architecture of the retromer cargo-recognition complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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