6LFL

Crystal structure of a class A GPCR

Summary for 6LFL

• Entry DOI: 10.2210/pdb6lfl/pdb
• Descriptor: C-X-C chemokine receptor type 2,GlgA glycogen synthase,C-X-C chemokine receptor type 2, 4-[[3,4-bis(oxidanylidene)-2-[[(1~{R})-1-(4-propan-2-ylfuran-2-yl)propyl]amino]cyclobuten-1-yl]amino]-~{N},~{N}-dimethyl-3-oxidanyl-pyridine-2-carboxamide (2 entities in total)
• Functional Keywords: g protein-coupled receptor, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 57121.34

Authors

Liu, Z.J.,Hua, T.,Liu, K.W.,Wu, L.J. (deposition date: 2019-12-03, release date: 2020-09-02, Last modification date: 2024-11-20)

Primary citation

Liu, K.,Wu, L.,Yuan, S.,Wu, M.,Xu, Y.,Sun, Q.,Li, S.,Zhao, S.,Hua, T.,Liu, Z.J.
Structural basis of CXC chemokine receptor 2 activation and signalling.
Nature, 585:135-140, 2020

PubMed Abstract: Chemokines and their receptors mediate cell migration, which influences multiple fundamental biological processes and disease conditions such as inflammation and cancer. Although ample effort has been invested into the structural investigation of the chemokine receptors and receptor-chemokine recognition, less is known about endogenous chemokine-induced receptor activation and G-protein coupling. Here we present the cryo-electron microscopy structures of interleukin-8 (IL-8, also known as CXCL8)-activated human CXC chemokine receptor 2 (CXCR2) in complex with G protein, along with a crystal structure of CXCR2 bound to a designed allosteric antagonist. Our results reveal a unique shallow mode of binding between CXCL8 and CXCR2, and also show the interactions between CXCR2 and G protein. Further structural analysis of the inactive and active states of CXCR2 reveals a distinct activation process and the competitive small-molecule antagonism of chemokine receptors. In addition, our results provide insights into how a G-protein-coupled receptor is activated by an endogenous protein molecule, which will assist in the rational development of therapeutics that target the chemokine system for better pharmacological profiles.

PubMed: 32610344
DOI: 10.1038/s41586-020-2492-5

Experimental method

X-RAY DIFFRACTION (3.2 Å)