1ML0

VIRAL CHEMOKINE BINDING PROTEIN M3 FROM MURINE GAMMAHERPESVIRUS68 IN COMPLEX WITH THE P8A VARIANT OF CC-CHEMOKINE MCP-1

Summary for 1ML0

• Entry DOI: 10.2210/pdb1ml0/pdb
• Related: 1DOK 1MKF
• Descriptor: M3 Protein, Small Inducible Cytokine (3 entities in total)
• Functional Keywords: herpesvirus, viral immune evasion, chemokine binding protein, decoy receptor, immune system
• Biological source: Murid herpesvirus 4 (Murine herpesvirus 68); More
• Cellular location: Secreted: P13500
• Total number of polymer chains: 2
• Total formula weight: 50481.20

Authors

Alexander, J.M.,Fremont, D.H. (deposition date: 2002-08-29, release date: 2002-11-13, Last modification date: 2024-11-06)

Primary citation

Alexander, J.M.,Nelson, C.A.,van Berkel, V.,Lau, E.K.,Studts, J.M.,Brett, T.J.,Speck, S.H.,Handel, T.M.,Virgin, H.W.,Fremont, D.H.
Structural Basis of Chemokine Sequestration by a Herpesvirus Decoy Receptor
Cell(Cambridge,Mass.), 111:343-356, 2002

PubMed Abstract: The M3 protein encoded by murine gamma herpesvirus68 (gamma HV68) functions as an immune system saboteur by the engagement of chemoattractant cytokines, thereby altering host antiviral inflammatory responses. Here we report the crystal structures of M3 both alone and in complex with the CC chemokine MCP-1. M3 is a two-domain beta sandwich protein with a unique sequence and topology, forming a tightly packed anti-parallel dimer. The stoichiometry of the MCP-1:M3 complex is 2:2, with two monomeric chemokines embedded at distal ends of the preassociated M3 dimer. Conformational flexibility and electrostatic complementation are both used by M3 to achieve high-affinity and broad-spectrum chemokine engagement. M3 also employs structural mimicry to promiscuously sequester chemokines, engaging conservative structural elements associated with both chemokine homodimerization and binding to G protein-coupled receptors.

PubMed: 12419245
DOI: 10.1016/S0092-8674(02)01007-3

Experimental method

X-RAY DIFFRACTION (2.8 Å)