View source for 6jpp


==Solution structure of ELMO1 RBD==
<StructureSection load='6jpp' size='340' side='right'caption='[[6jpp]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6jpp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6JPP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6JPP 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=6jpp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6jpp OCA], [https://pdbe.org/6jpp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6jpp RCSB], [https://www.ebi.ac.uk/pdbsum/6jpp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6jpp ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ELMO1_HUMAN ELMO1_HUMAN] Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in assocation with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1.<ref>PMID:11595183</ref> <ref>PMID:12134158</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The control of cell movement through manipulation of cytoskeletal structure has therapeutic prospects notably in the development of novel anti-metastatic drugs. In this study, we determine the structure of Ras-binding domain (RBD) of ELMO1, a protein involved in cytoskeletal regulation, both alone and in complex with the activator RhoG and verify its targetability through computational nanobody design. Using our dock-and-design approach optimized with native-like initial pose selection, we obtain Nb01, a detectable binder from scratch in the first-round design. An affinity maturation step guided by structure-activity relationship at the interface generates 23 Nb01 sequence variants and 17 of them show enhanced binding to ELMO1-RBD and are modeled to form major spatial overlaps with RhoG. The best binder, Nb29, inhibited ELMO1-RBD/RhoG interaction. Molecular dynamics simulation of the flexibility of CDR2 and CDR3 of Nb29 reveal the design of stabilizing mutations at the CDR-framework junctions potentially confers the affinity enhancement.

Targeting Ras-binding domain of ELMO1 by computational nanobody design.,Tam C, Kukimoto-Niino M, Miyata-Yabuki Y, Tsuda K, Mishima-Tsumagari C, Ihara K, Inoue M, Yonemochi M, Hanada K, Matsumoto T, Shirouzu M, Zhang KYJ Commun Biol. 2023 Mar 17;6(1):284. doi: 10.1038/s42003-023-04657-w. PMID:36932164<ref>PMID:36932164</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6jpp" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Kukimoto-Niino M]]
[[Category: Shirouzu M]]
[[Category: Tsuda K]]