4XT1

Structure of a nanobody-bound viral GPCR bound to human chemokine CX3CL1

Summary for 4XT1

• Entry DOI: 10.2210/pdb4xt1/pdb
• Related: 4XT3
• Descriptor: G-protein coupled receptor homolog US28, Fractalkine, nanobody 7, ... (8 entities in total)
• Functional Keywords: gpcr, chemokine, membrane protein, complex, viral protein-signalling protein complex, viral protein/signalling protein
• Biological source: Cytomegalovirus; More
• Cellular location: Host cell membrane; Multi-pass membrane protein: P69332; Cell membrane; Single-pass type I membrane protein. Processed fractalkine: Secreted: P78423
• Total number of polymer chains: 3
• Total formula weight: 69666.35

Authors

Burg, J.S.,Jude, K.M.,Waghray, D.,Garcia, K.C. (deposition date: 2015-01-22, release date: 2015-03-04, Last modification date: 2023-09-27)

Primary citation

Burg, J.S.,Ingram, J.R.,Venkatakrishnan, A.J.,Jude, K.M.,Dukkipati, A.,Feinberg, E.N.,Angelini, A.,Waghray, D.,Dror, R.O.,Ploegh, H.L.,Garcia, K.C.
Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor.
Science, 347:1113-1117, 2015

PubMed Abstract: Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state-like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor's inactive state.

PubMed: 25745166
DOI: 10.1126/science.aaa5026

Experimental method

X-RAY DIFFRACTION (2.886 Å)