- EMDB-39696: Orphan receptor GPRC5D in complex with scFv150-18 -
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基本情報
登録情報
データベース: EMDB / ID: EMD-39696
タイトル
Orphan receptor GPRC5D in complex with scFv150-18
マップデータ
試料
複合体: Complex of Orphan GPRC5D with scFv150-18
タンパク質・ペプチド: Soluble cytochrome b562,G-protein coupled receptor family C group 5 member D
タンパク質・ペプチド: scFv
キーワード
orphan receptor / GPRC5D complex / scFv / MEMBRANE PROTEIN
機能・相同性
機能・相同性情報
protein kinase activator activity / electron transport chain / G protein-coupled receptor activity / periplasmic space / electron transfer activity / receptor complex / iron ion binding / intracellular membrane-bounded organelle / heme binding / extracellular exosome / plasma membrane 類似検索 - 分子機能
ジャーナル: Nat Commun / 年: 2024 タイトル: The binding mechanism of an anti-multiple myeloma antibody to the human GPRC5D homodimer. 著者: Pengfei Yan / Xi Lin / Lijie Wu / Lu Xu / Fei Li / Junlin Liu / Fei Xu / 要旨: 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, ...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 distinct head-to-head homodimer arrangement and interface mainly involving TM4, setting it apart from other Class C homo- or hetero-dimers. Furthermore, we elucidate the binding site engaging a sizable extracellular domain on GPRC5D for scFv recognition. These insights not only unveil the distinctive dimer organization of this unconventional Class C GPCR but also hold the potential to advance drug development targeting GPRC5D for the treatment of multiple myeloma.