Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.0040005
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dc.titleStructure and function of A41, a vaccinia virus chemokine binding protein
dc.contributor.authorBahar M.W.
dc.contributor.authorKenyon J.C.
dc.contributor.authorPutz M.M.
dc.contributor.authorAbrescia N.G.A.
dc.contributor.authorPease J.E.
dc.contributor.authorWise E.L.
dc.contributor.authorStuart D.I.
dc.contributor.authorSmith G.L.
dc.contributor.authorGrimes J.M.
dc.date.accessioned2019-11-08T00:57:40Z
dc.date.available2019-11-08T00:57:40Z
dc.date.issued2008
dc.identifier.citationBahar M.W., Kenyon J.C., Putz M.M., Abrescia N.G.A., Pease J.E., Wise E.L., Stuart D.I., Smith G.L., Grimes J.M. (2008). Structure and function of A41, a vaccinia virus chemokine binding protein. PLoS Pathogens 4 (1) : 55-68. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.0040005
dc.identifier.issn15537366
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/161860
dc.description.abstractThe vaccinia virus (VACV) A41L gene encodes a secreted 30 kDa glycoprotein that is nonessential for virus replication but affects the host response to infection. The A41 protein shares sequence similarity with another VACV protein that binds CC chemokines (called vCKBP, or viral CC chemokine inhibitor, vCCI), and strains of VACV lacking the A41L gene induced stronger CD8+ T-cell responses than control viruses expressing A41. Using surface plasmon resonance, we screened 39 human and murine chemokines and identified CCL21, CCL25, CCL26 and CCL28 as A41 ligands, with Kds of between 8 nM and 118 nM. Nonetheless, A41 was ineffective at inhibiting chemotaxis induced by these chemokines, indicating it did not block the interaction of these chemokines with their receptors. However the interaction of A41 and chemokines was inhibited in a dose-dependent manner by heparin, suggesting that A41 and heparin bind to overlapping sites on these chemokines. To better understand the mechanism of action of A41 its crystal structure was solved to 1.9 � resolution. The protein has a globular ? sandwich structure similar to that of the poxvirus vCCI family of proteins, but there are notable structural differences, particularly in surface loops and electrostatic charge distribution. Structural modelling suggests that the binding paradigm as defined for the vCCI-chemokine interaction is likely to be conserved between A41 and its chemokine partners. Additionally, sequence analysis of chemokines binding to A41 identified a signature for A41 binding. The biological and structural data suggest that A41 functions by forming moderately strong (nM) interactions with certain chemokines, sufficient to interfere with chemokine-glycosaminoglycan interactions at the cell surface (?M-nM) and thereby to destroy the chemokine concentration gradient, but not strong enough to disrupt the (pM) chemokine-chemokine receptor interactions. � 2008 Bahar et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectbeta chemokine
dc.subjectbinding protein
dc.subjectchemokine CCL25
dc.subjectchemokine CCL28
dc.subjectchemokine inhibitor
dc.subjectchemokine inhibitor vCCI
dc.subjecteotaxin 3
dc.subjectglycosaminoglycan
dc.subjectheparin
dc.subjectprotein vCKBP
dc.subjectsecondary lymphoid tissue chemokine
dc.subjectunclassified drug
dc.subjectvirus protein A41
dc.subjectbeta chemokine
dc.subjectvirus protein
dc.subjectA41L gene
dc.subjectanimal cell
dc.subjectarticle
dc.subjectbinding site
dc.subjectCD8+ T lymphocyte
dc.subjectconcentration response
dc.subjectcontrolled study
dc.subjectcrystal structure
dc.subjectdose response
dc.subjectdrug mechanism
dc.subjecthuman
dc.subjectimmune response
dc.subjectligand binding
dc.subjectnonhuman
dc.subjectoptical resolution
dc.subjectprotein protein interaction
dc.subjectprotein secretion
dc.subjectprotein structure
dc.subjectsequence homology
dc.subjectstructure activity relation
dc.subjectsurface plasmon resonance
dc.subjectVaccinia virus
dc.subjectvirus gene
dc.subjectvirus replication
dc.subjectamino acid sequence
dc.subjectanimal
dc.subjectbiological model
dc.subjectchemistry
dc.subjectchemotaxis
dc.subjectcrystallization
dc.subjectcytology
dc.subjectimmunology
dc.subjectleukocyte
dc.subjectmetabolism
dc.subjectmolecular genetics
dc.subjectmouse
dc.subjectphysiology
dc.subjectprotein binding
dc.subjectprotein conformation
dc.subjectMurinae
dc.subjectPoxviridae
dc.subjectVaccinia virus
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectCD8-Positive T-Lymphocytes
dc.subjectChemokines, CC
dc.subjectChemotaxis
dc.subjectCrystallization
dc.subjectGlycosaminoglycans
dc.subjectHeparin
dc.subjectHumans
dc.subjectLeukocytes
dc.subjectMice
dc.subjectModels, Biological
dc.subjectMolecular Sequence Data
dc.subjectProtein Binding
dc.subjectProtein Conformation
dc.subjectStructure-Activity Relationship
dc.subjectVaccinia virus
dc.subjectViral Proteins
dc.typeArticle
dc.contributor.departmentMICROBIOLOGY AND IMMUNOLOGY
dc.description.doi10.1371/journal.ppat.0040005
dc.description.sourcetitlePLoS Pathogens
dc.description.volume4
dc.description.issue1
dc.description.page55-68
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