5CYW

Crystal Structure of Vaccinia Virus C7

Summary for 5CYW

• Entry DOI: 10.2210/pdb5cyw/pdb
• Related: 5CZ3
• Descriptor: Interferon antagonist C7, GLYCEROL (3 entities in total)
• Functional Keywords: host-range, beta-sandwich, poxvirus, vaccinia, viral protein
• Biological source: Vaccinia virus (strain Ankara) (VACV)
• Total number of polymer chains: 1
• Total formula weight: 18402.96

Authors

Krumm, B.E.,Meng, X.,Li, Y.,Xiang, Y.,Deng, J. (deposition date: 2015-07-30, release date: 2015-11-18, Last modification date: 2024-03-06)

Primary citation

Meng, X.,Krumm, B.,Li, Y.,Deng, J.,Xiang, Y.
Structural basis for antagonizing a host restriction factor by C7 family of poxvirus host-range proteins.
Proc.Natl.Acad.Sci.USA, 112:14858-14863, 2015

PubMed Abstract: Human sterile alpha motif domain-containing 9 (SAMD9) protein is a host restriction factor for poxviruses, but it can be overcome by some poxvirus host-range proteins that share homology with vaccinia virus C7 protein. To understand the mechanism of action for this important family of host-range factors, we determined the crystal structures of C7 and myxoma virus M64, a C7 family member that is unable to antagonize SAMD9. Despite their different functions and only 23% sequence identity, the two proteins have very similar overall structures, displaying a previously unidentified fold comprised of a compact 12-stranded antiparallel β-sandwich wrapped in two short α helices. Extensive structure-guided mutagenesis of C7 identified three loops clustered on one edge of the β sandwich as critical for viral replication and binding with SAMD9. The loops are characterized with functionally important negatively charged, positively charged, and hydrophobic residues, respectively, together forming a unique "three-fingered molecular claw." The key residues of the claw are not conserved in two C7 family members that do not antagonize SAMD9 but are conserved in distantly related C7 family members from four poxvirus genera that infect diverse mammalian species. Indeed, we found that all in the latter group of proteins bind SAMD9. Taken together, our data indicate that diverse mammalian poxviruses use a conserved molecular claw in a C7-like protein to target SAMD9 and overcome host restriction.

PubMed: 26578811
DOI: 10.1073/pnas.1515354112

Experimental method

X-RAY DIFFRACTION (2 Å)