7dxk
From Proteopedia
(Difference between revisions)
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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]] 4.10Å' 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]] 4.1Å</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®/PubMed®, 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: | + | [[Category: Synthetic construct]] |
| + | [[Category: Fernandez-Busnadiego R]] | ||
| + | [[Category: Guo Q]] | ||
Current revision
Human 128QHuntingtin-HAP40 complex structure
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