Structure-Function Analysis of Vaccinia Virus H7 Protein Reveals a Novel Phosphoinositide Binding Fold Essential for Poxvirus Replication

Kolli, Swapna; Meng, Xiangzhi; Wu, Xiang; Shengjuler, Djoshkun; Cameron, Craig E.; Xiang, Yan; Deng, Junpeng

doi:10.1128/jvi.03073-14

Structure-Function Analysis of Vaccinia Virus H7 Protein Reveals a Novel Phosphoinositide Binding Fold Essential for Poxvirus Replication

Journal Article · Tue Dec 02 23:00:00 EST 2014 · Journal of Virology

DOI:https://doi.org/10.1128/jvi.03073-14· OSTI ID:1208677

Kolli, Swapna ^[1]; Meng, Xiangzhi ^[2]; Wu, Xiang ^[2]; Shengjuler, Djoshkun ^[3]; Cameron, Craig E. ^[3]; Xiang, Yan ^[2]; Deng, Junpeng ^[1]

Oklahoma City Univ., OK (United States)
Univ. of Texas Health Science Center, San Antonio, TX (United States)
Pennsylvania State Univ., University Park, PA (United States)

Phosphoinositides and phosphoinositide binding proteins play a critical role in membrane and protein trafficking in eukaryotes. Their critical role in replication of cytoplasmic viruses has just begun to be understood. Poxviruses, a family of large cytoplasmic DNA viruses, rely on the intracellular membranes to develop their envelope, and poxvirus morphogenesis requires enzymes from the cellular phosphoinositide metabolic pathway. However, the role of phosphoinositides in poxvirus replication remains unclear, and no poxvirus proteins show any homology to eukaryotic phosphoinositide binding domains. Recently, a group of poxvirus proteins, termed viral membrane assembly proteins (VMAPs), were identified as essential for poxvirus membrane biogenesis. A key component of VMAPs is the H7 protein. Here we report the crystal structure of the H7 protein from vaccinia virus. The H7 structure displays a novel fold comprised of seven α-helices and a highly curved three-stranded antiparallel β-sheet. We identified a phosphoinositide binding site in H7, comprised of basic residues on a surface patch and the flexible C-terminal tail. These residues were found to be essential for viral replication and for binding of H7 to phosphatidylinositol-3-phosphate (PI3P) and phosphatidylinositol-4-phosphate (PI4P). Our studies suggest that phosphoinositide binding by H7 plays an essential role in poxvirus membrane biogenesis.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE

OSTI ID:: 1208677

Journal Information:: Journal of Virology, Journal Name: Journal of Virology Journal Issue: 4 Vol. 89; ISSN 0022-538X

Publisher:: American Society for MicrobiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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