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====
==Human 128QHuntingtin-HAP40 complex structure==
<StructureSection load='7dxk' size='340' side='right'caption='[[7dxk]]' scene=''>
<StructureSection load='7dxk' size='340' side='right'caption='[[7dxk]], [[Resolution|resolution]] 4.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
<table><tr><td colspan='2'>[[7dxk]] 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=7DXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DXK FirstGlance]. <br>
</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=7dxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dxk OCA], [https://pdbe.org/7dxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dxk RCSB], [https://www.ebi.ac.uk/pdbsum/7dxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dxk ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.1&#8491;</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=7dxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dxk OCA], [https://pdbe.org/7dxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dxk RCSB], [https://www.ebi.ac.uk/pdbsum/7dxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dxk ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/HAP40_HUMAN HAP40_HUMAN] Up-regulated in brain tissue from patients affected by Huntington's disease (at protein level) (PubMed:16476778). In a Huntington's disease mouse model overexpression of F8A1/F8A2/F8A3 impairs proteasome activity leading to the accumulation of mutant HTT and causes defective mitochondrial functions (PubMed:27815841, PubMed:29209146).<ref>PMID:16476778</ref> <ref>PMID:27815841</ref> <ref>PMID:29209146</ref>
== Function ==
[https://www.uniprot.org/uniprot/HAP40_HUMAN HAP40_HUMAN] RAB5A effector molecule that is involved in vesicular trafficking of early endosomes (PubMed:16476778). Mediates the recruitment of HTT by RAB5A onto early endosomes. The HTT-F8A1/F8A2/F8A3-RAB5A complex stimulates early endosomal interaction with actin filaments and inhibits interaction with microtubules, leading to the reduction of endosome motility (PubMed:16476778).<ref>PMID:16476778</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The abnormal amplification of a CAG repeat in the gene coding for huntingtin (HTT) leads to Huntington's disease (HD). At the protein level, this translates into the expansion of a polyglutamine (polyQ) stretch located at the HTT N terminus, which renders HTT aggregation prone by unknown mechanisms. Here we investigated the effects of polyQ expansion on HTT in a complex with its stabilizing interaction partner huntingtin-associated protein 40 (HAP40). Surprisingly, our comprehensive biophysical, crosslinking mass spectrometry and cryo-EM experiments revealed no major differences in the conformation of HTT-HAP40 complexes of various polyQ length, including 17QHTT-HAP40 (wild type), 46QHTT-HAP40 (typical polyQ length in HD patients), and 128QHTT-HAP40 (extreme polyQ length). Thus, HTT polyQ expansion does not alter the global conformation of HTT when associated with HAP40.
Pathological polyQ expansion does not alter the conformation of the Huntingtin-HAP40 complex.,Huang B, Guo Q, Niedermeier ML, Cheng J, Engler T, Maurer M, Pautsch A, Baumeister W, Stengel F, Kochanek S, Fernandez-Busnadiego R Structure. 2021 Aug 5;29(8):804-809.e5. doi: 10.1016/j.str.2021.04.003. Epub 2021 , Apr 27. PMID:33909994<ref>PMID:33909994</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dxk" style="background-color:#fffaf0;"></div>
==See Also==
*[[Huntingtin|Huntingtin]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Z-disk]]
[[Category: Synthetic construct]]
[[Category: Fernandez-Busnadiego R]]
[[Category: Guo Q]]
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