View source for 8gxl


==HUMAN SUGP1 433-577==
<StructureSection load='8gxl' size='340' side='right'caption='[[8gxl]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8gxl]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GXL 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]] 2.4&#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=8gxl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8gxl OCA], [https://pdbe.org/8gxl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8gxl RCSB], [https://www.ebi.ac.uk/pdbsum/8gxl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8gxl ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SUGP1_HUMAN SUGP1_HUMAN] Plays a role in pre-mRNA splicing.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
SF3B1 is the most frequently mutated spliceosomal gene in cancer. Several hotspot mutations are known to disrupt the interaction of SF3B1 with another splicing factor, SUGP1, resulting in the RNA missplicing that characterizes mutant SF3B1 cancers. Properties of SUGP1, especially the presence of a G-patch motif, a structure known to function by activating DEAH-box RNA helicases, suggest the requirement of such an enzyme in SUGP1 function in splicing. However, the identity of this putative helicase has remained an important unanswered question. Here, using a variety of protein-protein interaction assays, we identify DHX15 as the critical helicase. We further show that depletion of DHX15 or expression of any of several DHX15 mutants, including one implicated in acute myeloid leukemia, partially recapitulates the splicing defects of mutant SF3B1. Moreover, a DHX15-SUGP1 G-patch fusion protein is able to incorporate into the spliceosome to rescue the splicing defects of mutant SF3B1. We also present the crystal structure of the human DHX15-SUGP1 G-patch complex, which reveals the molecular basis of their direct interaction. Our data thus demonstrate that DHX15 is the RNA helicase that functions with SUGP1 and additionally provide important insight into how mutant SF3B1 disrupts splicing in cancer.

DHX15 is involved in SUGP1-mediated RNA missplicing by mutant SF3B1 in cancer.,Zhang J, Huang J, Xu K, Xing P, Huang Y, Liu Z, Tong L, Manley JL Proc Natl Acad Sci U S A. 2022 Dec 6;119(49):e2216712119. doi: , 10.1073/pnas.2216712119. Epub 2022 Dec 2. PMID:36459648<ref>PMID:36459648</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8gxl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Tong L]]
[[Category: Xu K]]