8uek

Solution structure of ACKR3-targeting nanobody VUN701

spinqualitylabelsall models 8uek Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8uek is a 1 chain structure with sequence from Lama glama. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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