View source for 6xsa


==Crystal structure of human Vps29 complexed with RaPID-derived cyclic peptide RT-L2==
<StructureSection load='6xsa' size='340' side='right'caption='[[6xsa]], [[Resolution|resolution]] 1.83&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xsa]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6XSA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XSA 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]] 1.83&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=48V:{[(2R)-2,3-DIAMINO-3-OXOPROPYL]SULFANYL}ACETIC+ACID'>48V</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6xsa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xsa OCA], [https://pdbe.org/6xsa PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xsa RCSB], [https://www.ebi.ac.uk/pdbsum/6xsa PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xsa ProSAT]</span></td></tr>
</table>
== 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The retromer complex (Vps35-Vps26-Vps29) is essential for endosomal membrane trafficking and signaling. Mutation of the retromer subunit Vps35 causes late-onset Parkinson's disease, while viral and bacterial pathogens can hijack the complex during cellular infection. To modulate and probe its function, we have created a novel series of macrocyclic peptides that bind retromer with high affinity and specificity. Crystal structures show that most of the cyclic peptides bind to Vps29 via a Pro-Leu-containing sequence, structurally mimicking known interactors such as TBC1D5 and blocking their interaction with retromer in vitro and in cells. By contrast, macrocyclic peptide RT-L4 binds retromer at the Vps35-Vps26 interface and is a more effective molecular chaperone than reported small molecules, suggesting a new therapeutic avenue for targeting retromer. Last, tagged peptides can be used to probe the cellular localization of retromer and its functional interactions in cells, providing novel tools for studying retromer function.

De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal trafficking complex.,Chen KE, Guo Q, Hill TA, Cui Y, Kendall AK, Yang Z, Hall RJ, Healy MD, Sacharz J, Norwood SJ, Fonseka S, Xie B, Reid RC, Leneva N, Parton RG, Ghai R, Stroud DA, Fairlie DP, Suga H, Jackson LP, Teasdale RD, Passioura T, Collins BM Sci Adv. 2021 Dec 3;7(49):eabg4007. doi: 10.1126/sciadv.abg4007. Epub 2021 Dec 1. PMID:34851660<ref>PMID:34851660</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6xsa" style="background-color:#fffaf0;"></div>

==See Also==
*[[Vacuolar protein sorting-associated protein 3D structures|Vacuolar protein sorting-associated protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Chen K-E]]
[[Category: Collins BM]]
[[Category: Guo Q]]