View source for 7bii


==Crystal structure of Nematocida HUWE1==
<StructureSection load='7bii' size='340' side='right'caption='[[7bii]], [[Resolution|resolution]] 3.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7bii]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nematocida_sp._ERTm5 Nematocida sp. ERTm5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BII OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7BII 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]] 3.037&#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=7bii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bii OCA], [https://pdbe.org/7bii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7bii RCSB], [https://www.ebi.ac.uk/pdbsum/7bii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7bii ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A177ELV2_9MICR A0A177ELV2_9MICR] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
HUWE1 is a universal quality-control E3 ligase that marks diverse client proteins for proteasomal degradation. Although the giant HECT enzyme is an essential component of the ubiquitin-proteasome system closely linked with severe human diseases, its molecular mechanism is little understood. Here, we present the crystal structure of Nematocida HUWE1, revealing how a single E3 enzyme has specificity for a multitude of unrelated substrates. The protein adopts a remarkable snake-like structure, where the C-terminal HECT domain heads an extended alpha-solenoid body that coils in on itself and houses various protein-protein interaction modules. Our integrative structural analysis shows that this ring structure is highly dynamic, enabling the flexible HECT domain to reach protein targets presented by the various acceptor sites. Together, our data demonstrate how HUWE1 is regulated by its unique structure, adapting a promiscuous E3 ligase to selectively target unassembled orphan proteins.

HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain.,Grabarczyk DB, Petrova OA, Deszcz L, Kurzbauer R, Murphy P, Ahel J, Vogel A, Gogova R, Faas V, Kordic D, Schleiffer A, Meinhart A, Imre R, Lehner A, Neuhold J, Bader G, Stolt-Bergner P, Bottcher J, Wolkerstorfer B, Fischer G, Grishkovskaya I, Haselbach D, Kessler D, Clausen T Nat Chem Biol. 2021 Oct;17(10):1084-1092. doi: 10.1038/s41589-021-00831-5. Epub, 2021 Jul 22. PMID:34294896<ref>PMID:34294896</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7bii" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Nematocida sp. ERTm5]]
[[Category: Clausen T]]
[[Category: Grabarczyk DB]]
[[Category: Kessler D]]
[[Category: Meinhart A]]
[[Category: Petrova OA]]