Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Vaccinia virus (VACV), the smallpox vaccine, encodes many proteins that subvert the host immune response. One of these, cytokine response modifier E (CrmE), is secreted by infected cells and protects these cells from apoptotic challenge by tumour necrosis factor alpha (TNFalpha). We have expressed recombinant CrmE from VACV strain Lister in Escherichia coli, shown that the purified protein is monomeric in solution and competent to bind TNFalpha, and solved the structure to 2.0 A resolution. This is the first structure of a virus-encoded tumour necrosis factor receptor (TNFR). CrmE shares significant sequence similarity with mammalian type 2 TNF receptors (TNFSFR1B, p75; TNFR type 2). The structure confirms that CrmE adopts the canonical TNFR fold but only one of the two "ligand-binding" loops of TNFRSF1A is conserved in CrmE, suggesting a mechanism for the higher affinity of poxvirus TNFRs for TNFalpha over lymphotoxin-alpha. The roles of dimerisation and pre-ligand-assembly domains (PLADs) in poxvirus and mammalian TNFR activity are discussed.

Original publication

DOI

10.1016/j.jmb.2007.06.082

Type

Journal article

Journal

J Mol Biol

Publication Date

21/09/2007

Volume

372

Pages

660 - 671

Keywords

Amino Acid Sequence, Crystallography, X-Ray, Humans, Hydrophobic and Hydrophilic Interactions, Ligands, Models, Molecular, Molecular Sequence Data, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Recombinant Proteins, Tumor Necrosis Factor-alpha, Vaccinia virus, Viral Proteins