SUPPLEMENTARY INFORMATIONIn format provided by Felix and Savvides (doi:10.1038/nri.2016.134)
Supplementary Figure 2: Herpesvirus-encoded and poxvirus-encoded binding proteins that do not have host counterparts.(A)Glycoprotein G (gG) is a chemokine-binding protein (CKBP) encoded by α-herpesviruses and is the prototypic member of the type IV CKBP family. gG inhibits both receptor and glycosaminoglycan (GAG) binding of a broad range of C-, CC- and CXC- chemokines. Human cytomegalovirus encodes a secreted CKBP termed pUL21.5, which selectively binds to CC-chemokine ligand 5(CCL5). R17 is a secreted CKBP that is encoded by rodent herpesvirus Peru. R17 binds and inhibits C- and CC-chemokines, and can simultaneously interact with GAGs on the cell surface. The M3 protein encoded by murine γ-herpesvirus 68 is a chemokine decoy receptor of the type III CKBPfamily and forms dimers. M3 inhibits receptor and GAG binding of several C-, CC-, CXC- and CX3C chemokines. Inset I shows the structural relatedness of the N- and C-terminal domains of M3 to diphtheriatoxin and a type V immunoglobulin (Ig) fold.(B)The CPXV203 protein encoded by cowpox virus is a poxvirus immune evasion (PIE) family member (formerly known as the type II CKBP family) that binds to MHC class I and prevents MHC class I-mediated antigen presentation on infected cells. (C) Several poxviruses encode a variant of viral CC-chemokine inhibitor (vCCI), which is a secreted chemokine decoy receptor and the prototypic member of the PIE family. vCCI binds to several CC-chemokines, and inhibits both receptor and GAG binding. The A41 protein encoded by vaccinia virus is a PIE family member that binds CC-chemokines with low affinity. A41 does not directly inhibit chemokine signalling but rather interferes with chemokine binding to GAGs. The C-terminal SECRET domain present in CrmB and CrmD has a similar fold to vCCI and A41, and is also a PIE member. The SECRET domain binds some C-, CC- and CXC-chemokines, and blocks receptor and GAG binding. Orf virus (ORFV) encodes two members of the PIE family termed ORFV CKBP and ORFV GIF. ORFV CKBP binds C-, CC- and CXC-chemokines, and blocks receptor and GAG binding. ORFV GIF, on the other hand, is a cytokine decoy receptor that inhibits both GM-CSF and IL-2 signalling. Figure based on Research Collaboratory for Structural Bioinformatics Protein Data Bank entries 2NZ1, 1DDT, 1IGT, 2FFK, 2VGA, 1G2S, 3ON9, 4ZK9, 4HKJ and 5D28. β2M, β2microglobulin; CX3CL1, CX3C-chemokine ligand 1; GM-CSF, Granulocyte-macrophage colony-stimulating factor; IL-2, Interleukin 2.
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