View source for 9ckx


==Crystal structure of Dsk2 Sti1 domain bound to a transmembrane domain==
<StructureSection load='9ckx' size='340' side='right'caption='[[9ckx]], [[Resolution|resolution]] 1.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ckx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Metschnikowia_bicuspidata Metschnikowia bicuspidata] and [https://en.wikipedia.org/wiki/Myxococcus_xanthus Myxococcus xanthus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9CKX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9CKX 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]] 1.98&#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=9ckx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ckx OCA], [https://pdbe.org/9ckx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ckx RCSB], [https://www.ebi.ac.uk/pdbsum/9ckx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ckx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0AA46P9Z6_MYXXA A0AA46P9Z6_MYXXA] [https://www.uniprot.org/uniprot/A0A1A0HF11_9ASCO A0A1A0HF11_9ASCO] [https://www.uniprot.org/uniprot/VAMP2_HUMAN VAMP2_HUMAN] Involved in the targeting and/or fusion of transport vesicles to their target membrane.
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== Publication Abstract from PubMed ==
Ubiquilins are a family of cytosolic proteins that ferry ubiquitinated substrates to the proteasome for degradation. Recent work has demonstrated that Ubiquilins can also act as molecular chaperones, utilizing internal Sti1 domains to directly bind to hydrophobic sequences. Ubiquilins are associated with several neurodegenerative diseases with point mutations in UBQLN2 causing dominant, X-linked Amyotrophic Lateral Sclerosis (ALS). The molecular basis of Ubiquilin chaperone activity and how ALS mutations in the Sti1 domains affect Ubiquilin activity are poorly understood. This study presents the first crystal structure of the Sti1 domain from a fungal Ubiquilin homolog bound to a transmembrane domain (TMD). The structure reveals that two Sti1 domains form a head-to-head dimer, creating a hydrophobic cavity that accommodates two TMDs. Mapping the UBQLN2 sequence onto the structure shows that several ALS mutations are predicted to disrupt the hydrophobic groove. Using a newly developed competitive binding assay, we show that Ubiquilins preferentially bind to hydrophobic substrates with low helical propensity, motifs that are enriched in both substrates and in Ubiquilins. This study provides insights into the molecular and structural basis for Ubiquilin substrate binding, with broad implications for the role of the Sti1 domain in phase separation and ALS.

The structural and biophysical basis of substrate binding to the hydrophobic groove in Ubiquilin Sti1 domains.,Onwunma J, Binsabaan S, Allen SP, Sankaran B, Wohlever ML bioRxiv [Preprint]. 2024 Jul 10:2024.07.10.602902. doi: , 10.1101/2024.07.10.602902. PMID:39026758<ref>PMID:39026758</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9ckx" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Metschnikowia bicuspidata]]
[[Category: Myxococcus xanthus]]
[[Category: Binsabaan S]]
[[Category: Sankaran B]]
[[Category: Wohlever ML]]