2NYZ

Viral Chemokine Binding Protein M3 From Murine Gammaherpesvirus68 In Complex With The C- Chemokine XCL1

Summary for 2NYZ

• Entry DOI: 10.2210/pdb2nyz/pdb
• Related: 1MKF 1ML0 2nz1
• Descriptor: Hypothetical protein GAMMAHV.M3, Lymphotactin (3 entities in total)
• Functional Keywords: viral decoy receptor, chemokine, protein-protein complex, viral protein-cytokine complex, viral protein/cytokine
• Biological source: Murid herpesvirus 4 (Murine herpesvirus 68); More
• Cellular location: Secreted: P47992
• Total number of polymer chains: 4
• Total formula weight: 104226.04

Authors

Alexander-Brett, J.M.,Fremont, D.H. (deposition date: 2006-11-21, release date: 2007-12-25, Last modification date: 2024-11-13)

Primary citation

Alexander-Brett, J.M.,Fremont, D.H.
Dual GPCR and GAG mimicry by the M3 chemokine decoy receptor.
J.Exp.Med., 204:3157-3172, 2007

PubMed Abstract: Viruses have evolved a myriad of evasion strategies focused on undermining chemokine-mediated immune surveillance, exemplified by the mouse gamma-herpesvirus 68 M3 decoy receptor. Crystal structures of M3 in complex with C chemokine ligand 1/lymphotactin and CC chemokine ligand 2/monocyte chemoattractant protein 1 reveal that invariant chemokine features associated with G protein-coupled receptor binding are primarily recognized by the decoy C-terminal domain, whereas the N-terminal domain (NTD) reconfigures to engage divergent basic residue clusters on the surface of chemokines. Favorable electrostatic forces dramatically enhance the association kinetics of chemokine binding by M3, with a primary role ascribed to acidic NTD regions that effectively mimic glycosaminoglycan interactions. Thus, M3 employs two distinct mechanisms of chemical imitation to potently sequester chemokines, thereby inhibiting chemokine receptor binding events as well as the formation of chemotactic gradients necessary for directed leukocyte trafficking.

PubMed: 18070938
DOI: 10.1084/jem.20071677

Experimental method

X-RAY DIFFRACTION (2.6 Å)