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The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer

Nat Commun. 2024-06; 
Pengfei Yan , Xi Lin , Lijie Wu , Lu Xu , Fei Li , Junlin Liu , Fei Xu
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Gene Synthesis The gene of human GPRC5D-WT (UniProt ID: Q9NZD1) was synthesized by GenScript and subcloned into the expression vector pFastbac1. Get A Quote

摘要

GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for therapeutic interventions, including monoclonal antibodies, CAR-T cells, and T-cell engagers. Despite its therapeutic potential, the insufficient understanding regarding of the receptor's structure and antibody recognition mechanism has impeded the progress of effective therapeutic development. Here, we present the structure of GPRC5D in complex with a preclinical-stage single-chain antibody (scFv). Our structural analysis reveals that the GPRC5D presents a close resemblance to the typical Class C GPCRs in the transmembrane region. We identify a d... More

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