8JPS

Structure of Duffy Antigen Receptor for Chemokines (DARC)/ACKR1 in complex with the chemokine, CCL7 (Composite map)

8JPS の概要

• エントリーDOI: 10.2210/pdb8jps/pdb
• EMDBエントリー: 36488
• 分子名称: Atypical chemokine receptor 1, C-C motif chemokine 7 (2 entities in total)
• 機能のキーワード: gpcr, 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: 4
• 化学式量合計: 71336.85

構造登録者

Banerjee, R.,Khanppnavar, B.,Maharana, J.,Saha, S.,Korkhov, V.M.,Shukla, A.K. (登録日: 2023-06-12, 公開日: 2024-07-31, 最終更新日: 2024-10-30)

主引用文献

Saha, S.,Khanppnavar, B.,Maharana, J.,Kim, H.,Carino, C.M.C.,Daly, C.,Houston, S.,Sharma, S.,Zaidi, N.,Dalal, A.,Mishra, S.,Ganguly, M.,Tiwari, D.,Kumari, P.,Jhingan, G.D.,Yadav, P.N.,Plouffe, B.,Inoue, A.,Chung, K.Y.,Banerjee, R.,Korkhov, V.M.,Shukla, A.K.
Molecular mechanism of distinct chemokine engagement and functional divergence of the human Duffy antigen receptor.
Cell, 187:4751-4769.e25, 2024

PubMed Abstract: The Duffy antigen receptor is a seven-transmembrane (7TM) protein expressed primarily at the surface of red blood cells and displays strikingly promiscuous binding to multiple inflammatory and homeostatic chemokines. It serves as the basis of the Duffy blood group system in humans and also acts as the primary attachment site for malarial parasite Plasmodium vivax and pore-forming toxins secreted by Staphylococcus aureus. Here, we comprehensively profile transducer coupling of this receptor, discover potential non-canonical signaling pathways, and determine the cryoelectron microscopy (cryo-EM) structure in complex with the chemokine CCL7. The structure reveals a distinct binding mode of chemokines, as reflected by relatively superficial binding and a partially formed orthosteric binding pocket. We also observe a dramatic shortening of TM5 and 6 on the intracellular side, which precludes the formation of the docking site for canonical signal transducers, thereby providing a possible explanation for the distinct pharmacological and functional phenotype of this receptor.

PubMed: 39089252
DOI: 10.1016/j.cell.2024.07.005

実験手法

ELECTRON MICROSCOPY (3.65 Å)