8DJG

ADGRL3-lectin domain in complex with an activating synthetic antibody fragment

8DJG の概要

• エントリーDOI: 10.2210/pdb8djg/pdb
• 分子名称: sAB Heavy Chain, sAB Light Chain, Isoform 2 of Adhesion G protein-coupled receptor L3, ... (7 entities in total)
• 機能のキーワード: adhesion gpcr, lectin domain, sab, signaling protein, signaling protein-immune system complex, signaling protein/immune system
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 121717.78

構造登録者

Kordon, S.P.,Bandekar, S.J.,Arac, D. (登録日: 2022-06-30, 公開日: 2023-02-15, 最終更新日: 2024-10-09)

主引用文献

Kordon, S.P.,Dutka, P.,Adamska, J.M.,Bandekar, S.J.,Leon, K.,Erramilli, S.K.,Adams, B.,Li, J.,Kossiakoff, A.A.,Arac, D.
Isoform- and ligand-specific modulation of the adhesion GPCR ADGRL3/Latrophilin3 by a synthetic binder.
Nat Commun, 14:635-635, 2023

PubMed Abstract: Adhesion G protein-coupled receptors (aGPCRs) are cell-surface proteins with large extracellular regions that bind to multiple ligands to regulate key biological functions including neurodevelopment and organogenesis. Modulating a single function of a specific aGPCR isoform while affecting no other function and no other receptor is not trivial. Here, we engineered an antibody, termed LK30, that binds to the extracellular region of the aGPCR ADGRL3, and specifically acts as an agonist for ADGRL3 but not for its isoform, ADGRL1. The LK30/ADGRL3 complex structure revealed that the LK30 binding site on ADGRL3 overlaps with the binding site for an ADGRL3 ligand - teneurin. In cellular-adhesion assays, LK30 specifically broke the trans-cellular interaction of ADGRL3 with teneurin, but not with another ADGRL3 ligand - FLRT3. Our work provides proof of concept for the modulation of isoform- and ligand-specific aGPCR functions using unique tools, and thus establishes a foundation for the development of fine-tuned aGPCR-targeted therapeutics.

PubMed: 36746957
DOI: 10.1038/s41467-023-36312-7

実験手法

X-RAY DIFFRACTION (2.65 Å)