title: Structural basis of chemokine sequestration by a herpesvirus decoy receptor.
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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Alexander
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Nelson
authors.forename: Victor
authors.initials: V
authors.lastname: van Berkel
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Lau
authors.forename: Joey M
authors.initials: JM
authors.lastname: Studts
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Brett
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Speck
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Handel
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
authors.forename: Daved H
authors.initials: DH
authors.lastname: Fremont
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018932:Chemokine CCL2 / Q000737:chemistry*; D019281:Dimerization; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid; D012996:Solutions; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D018932:Chemokine CCL2; C118862:M3 protein, Murine gammaherpesvirus; D011991:Receptors, Virus; D012996:Solutions; D014764:Viral Proteins