View source for 8be5


==Crystal structure of SOS1-KRasG12V-Nanobody22-Nanobody75==
<StructureSection load='8be5' size='340' side='right'caption='[[8be5]], [[Resolution|resolution]] 3.13&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8be5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BE5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BE5 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]] 3.13&#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=8be5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8be5 OCA], [https://pdbe.org/8be5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8be5 RCSB], [https://www.ebi.ac.uk/pdbsum/8be5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8be5 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SOS1_HUMAN SOS1_HUMAN] Defects in SOS1 are the cause of gingival fibromatosis 1 (GGF1) [MIM:[https://omim.org/entry/135300 135300]; also known as GINGF1. Gingival fibromatosis is a rare overgrowth condition characterized by a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of maxillary and mandibular keratinized gingiva. GGF1 is usually transmitted as an autosomal dominant trait, although sporadic cases are common.<ref>PMID:11868160</ref>   Defects in SOS1 are the cause of Noonan syndrome type 4 (NS4) [MIM:[https://omim.org/entry/610733 610733]. NS4 is an autosomal dominant disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS4 is associated with juvenile myelomonocytic leukemia (JMML). SOS1 mutations engender a high prevalence of pulmonary valve disease; atrial septal defects are less common.<ref>PMID:17143285</ref> <ref>PMID:17143282</ref> <ref>PMID:19020799</ref> <ref>PMID:19438935</ref> <ref>PMID:20683980</ref> <ref>PMID:20673819</ref> <ref>PMID:19953625</ref> <ref>PMID:21387466</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SOS1_HUMAN SOS1_HUMAN] Promotes the exchange of Ras-bound GDP by GTP.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein-protein interactions (PPIs) are central in cell metabolism but research tools for the structural and functional characterization of these PPIs are often missing. Here we introduce broadly applicable immunization (Cross-link PPIs and immunize llamas, ChILL) and selection strategies (Display and co-selection, DisCO) for the discovery of diverse nanobodies that either stabilize or disrupt PPIs in a single experiment. We apply ChILL and DisCO to identify competitive, connective, or fully allosteric nanobodies that inhibit or facilitate the formation of the SOS1*RAS complex and modulate the nucleotide exchange rate on this pivotal GTPase in vitro as well as RAS signalling in cellulo. One of these connective nanobodies fills a cavity that was previously identified as the binding pocket for a series of therapeutic lead compounds. The long complementarity-determining region (CDR3) that penetrates this binding pocket serves as pharmacophore for extending the repertoire of potential leads.

Allosteric nanobodies to study the interactions between SOS1 and RAS.,Fischer B, Uchanski T, Sheryazdanova A, Gonzalez S, Volkov AN, Brosens E, Zogg T, Kalichuk V, Ballet S, Versees W, Sablina AA, Pardon E, Wohlkonig A, Steyaert J Nat Commun. 2024 Jul 23;15(1):6214. doi: 10.1038/s41467-024-50349-2. PMID:39043660<ref>PMID:39043660</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8be5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Son of sevenless 3D structures|Son of sevenless 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Fischer B]]
[[Category: Steyaert J]]
[[Category: Wohlkonig A]]