7SK4

Cryo-EM structure of ACKR3 in complex with chemokine N-terminal mutant CXCL12_LRHQ, an intracellular Fab, and an extracellular Fab

7SK4 の概要

• エントリーDOI: 10.2210/pdb7sk4/pdb
• EMDBエントリー: 25172
• 分子名称: Atypical chemokine receptor 3, Stromal cell-derived factor 1, CID25 Fab light chain, ... (7 entities in total)
• 機能のキーワード: atypical chemokine receptor, membrane protein, signaling protein, signaling protein-immune system complex, signaling protein/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 152003.14

構造登録者

Yen, Y.C.,Schafer, C.T.,Gustavsson, M.,Handel, T.M.,Tesmer, J.J.G. (登録日: 2021-10-19, 公開日: 2022-07-27)

主引用文献

Yen, Y.C.,Schafer, C.T.,Gustavsson, M.,Eberle, S.A.,Dominik, P.K.,Deneka, D.,Zhang, P.,Schall, T.J.,Kossiakoff, A.A.,Tesmer, J.J.G.,Handel, T.M.
Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias.
Sci Adv, 8:eabn8063-eabn8063, 2022

PubMed Abstract: Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward β-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs.

PubMed: 35857509
DOI: 10.1126/sciadv.abn8063

実験手法

ELECTRON MICROSCOPY (3.3 Å)