View source for 8uek


==Solution structure of ACKR3-targeting nanobody VUN701==
<StructureSection load='8uek' size='340' side='right'caption='[[8uek]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8uek]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8UEK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8UEK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=8uek FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8uek OCA], [https://pdbe.org/8uek PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8uek RCSB], [https://www.ebi.ac.uk/pdbsum/8uek PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8uek ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
G protein-coupled receptors (GPCRs) are pivotal therapeutic targets, but their complex structure poses challenges for effective drug design. Nanobodies, or single-domain antibodies, have emerged as a promising therapeutic strategy to target GPCRs, offering advantages over traditional small molecules and antibodies. However, an incomplete understanding of the structural features enabling GPCR-nanobody interactions has limited their development. In this study, we investigate VUN701, a nanobody antagonist targeting the atypical chemokine receptor 3 (ACKR3). We determine that an extended CDR3 loop is required for ACKR3 binding. Uncommon in most nanobodies, an extended CDR3 is prevalent in GPCR-targeting nanobodies. Combining experimental and computational approaches, we map an inhibitory ACKR3-VUN701 interface and define a distinct conformational mechanism for GPCR inactivation. Our results provide insights into class A GPCR-nanobody selectivity and suggest a strategy for the development of these new therapeutic tools.

Structural basis for selectivity and antagonism in extracellular GPCR-nanobodies.,Schlimgen RR, Peterson FC, Heukers R, Smit MJ, McCorvy JD, Volkman BF Nat Commun. 2024 May 30;15(1):4611. doi: 10.1038/s41467-024-49000-x. PMID:38816420<ref>PMID:38816420</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
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== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Peterson FC]]
[[Category: Schlimgen RR]]
[[Category: Volkman BF]]