title: Role for the conserved N-terminal cysteines in the anti-chemokine activities by the chemokine-like protein MC148R1 encoded by Molluscum contagiosum virus.
abstract: Molluscum contagiosum poxvirus (MCV) type 1 and type 2 encode two chemokine-like proteins MC148R1 and MC148R2. It is believed that MC148R proteins function by blocking the inflammatory response. However, the mechanism of the proposed biological activities of MC148R proteins and the role of the additional C-terminal cysteines that do not exist in other chemokines are not understood. Here, we demonstrated in two different assay systems that His-tagged MC148R1 displaces the interaction between CXCL12α and CXCR4. The N-terminal cysteines but not the additional C-terminal cysteines modulate this displacement. His-tagged MC148R1 blocked both CXCL12α-mediated and MIP-1α-mediated chemotaxis. In contrast, MC148R2 blocked MIP-1α-mediated but not CXCL12α-mediated chemotaxis. Immunoprecipitation by antibodies to MC148R1 or CXCL12α followed by immunoblotting and detection by antibodies to the other protein demonstrated physical interaction of His-tagged CXCL12α and His-tagged MC148R1. Interaction with chemokines might mask the receptor interaction site resulting in decreased binding and impairment of the biological activities.
authors.affiliation: Department of Biomedical Sciences, Center of Excellence for Infectious Diseases, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA.
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Jin
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Altenburg
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Hossain
authors.forename: Ghalib
authors.initials: G
authors.lastname: Alkhatib
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors*; D019742:Chemokines, CC / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002633:Chemotaxis; D003545:Cysteine / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008969:Molecular Sequence Data; D008977:Molluscum contagiosum virus / Q000276:immunology / Q000472:pathogenicity*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*; D016415:Sequence Alignment; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019742:Chemokines, CC; C435144:MC148 protein, poxvirus molluscum contagiosum; D019718:Receptors, CXCR4; D014764:Viral Proteins; D003545:Cysteine