View source for 6xs8


==Crystal structure of Chaetomium thermophilum Vps29 complexed with RaPID-derived cyclic peptide RT-D3==
<StructureSection load='6xs8' size='340' side='right'caption='[[6xs8]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6xs8]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum Chaetomium thermophilum] 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=6XS8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6XS8 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]] 1.9500985&#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=DTY:D-TYROSINE'>DTY</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=6xs8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6xs8 OCA], [https://pdbe.org/6xs8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6xs8 RCSB], [https://www.ebi.ac.uk/pdbsum/6xs8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6xs8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/G0RZB5_CHATD G0RZB5_CHATD] 
<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 6xs8" 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: Chaetomium thermophilum]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Chen K-E]]
[[Category: Collins BM]]
[[Category: Guo Q]]