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Myxoma virus immunomodulatory protein M156R is a structural mimic of eukaryotic translation initiation factor eIF2alpha.

Ramelot TA, Cort JR, Yee AA, Liu F, Goshe MB, Edwards AM, Smith RD, Arrowsmith CH, Dever TE, Kennedy MA
J Mol Biol 322 943-54 (2002)
Related entries: 1jcu, 1jdq, 1je3, 1jrm, 1jw2, 1jw3, 1ryj, 1ryk

Cited: 38 times
EuropePMC logo PMID: 12367520

Abstract

Phosphorylation of the translation initiation factor eIF2 on Ser51 of its alpha subunit is a key event for regulation of protein synthesis in all eukaryotes. M156R, the product of the myxoma virus M156R open reading frame, has sequence similarity to eIF2alpha as well as to a family of viral proteins that bind to the interferon-induced protein kinase PKR and inhibit phosphorylation of eIF2alpha. In this study, we demonstrate that, like eIF2alpha. M156R is an efficient substrate for phosphorylation by PKR and can compete with eIF2alpha. To gain insights into the substrate specificity of the eIF2alpha kinases, we have determined the nuclear magnetic resonance (NMR) structure of M156R, the first structure of a myxoma virus protein. The fold consists of a five-stranded antiparallel beta-barrel with two of the strands connected by a loop and an alpha-helix. The similarity between M156R and the beta-barrel structure in the N terminus of eIF2alpha suggests that the viral homologs mimic eIF2alpha structure in order to compete for binding to PKR. A homology-modeled structure of the well-studied vaccinia virus K3L was generated on the basis of alignment with M156R. Comparison of the structures of the K3L model, M156R, and human eIF2alpha indicated that residues important for binding to PKR are located at conserved positions on the surface of the beta-barrel and in the mobile loop, identifying the putative PKR recognition motif.

Reviews - 1jjg mentioned but not cited (1)

  1. Poxvirus proteomics and virus-host protein interactions. Van Vliet K, Mohamed MR, Zhang L, Villa NY, Werden SJ, Liu J, McFadden G. Microbiol Mol Biol Rev 73 730-749 (2009)

Articles - 1jjg mentioned but not cited (2)

  1. An NMR approach to structural proteomics. Yee A, Chang X, Pineda-Lucena A, Wu B, Semesi A, Le B, Ramelot T, Lee GM, Bhattacharyya S, Gutierrez P, Denisov A, Lee CH, Cort JR, Kozlov G, Liao J, Finak G, Chen L, Wishart D, Lee W, McIntosh LP, Gehring K, Kennedy MA, Edwards AM, Arrowsmith CH. Proc Natl Acad Sci U S A 99 1825-1830 (2002)
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Reviews citing this publication (18)

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  2. Cellular autophagy: surrender, avoidance and subversion by microorganisms. Kirkegaard K, Taylor MP, Jackson WT. Nat Rev Microbiol 2 301-314 (2004)
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  4. Tinkering with translation: protein synthesis in virus-infected cells. Walsh D, Mathews MB, Mohr I. Cold Spring Harb Perspect Biol 5 a012351 (2013)
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  7. Current Approaches for Combination Therapy of Cancer: The Role of Immunogenic Cell Death. Asadzadeh Z, Safarzadeh E, Safaei S, Baradaran A, Mohammadi A, Hajiasgharzadeh K, Derakhshani A, Argentiero A, Silvestris N, Baradaran B. Cancers (Basel) 12 E1047 (2020)
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  1. Rapid evolution of protein kinase PKR alters sensitivity to viral inhibitors. Rothenburg S, Seo EJ, Gibbs JS, Dever TE, Dittmar K. Nat Struct Mol Biol 16 63-70 (2009)
  2. A hybridoma-based in vitro translation system that efficiently synthesizes glycoproteins. Mikami S, Kobayashi T, Yokoyama S, Imataka H. J Biotechnol 127 65-78 (2006)
  3. Myxoma virus M156 is a specific inhibitor of rabbit PKR but contains a loss-of-function mutation in Australian virus isolates. Peng C, Haller SL, Rahman MM, McFadden G, Rothenburg S. Proc Natl Acad Sci U S A 113 3855-3860 (2016)
  4. Protein kinase PKR mutants resistant to the poxvirus pseudosubstrate K3L protein. Seo EJ, Liu F, Kawagishi-Kobayashi M, Ung TL, Cao C, Dar AC, Sicheri F, Dever TE. Proc Natl Acad Sci U S A 105 16894-16899 (2008)
  5. An efficient in vitro translation system from mammalian cells lacking the translational inhibition caused by eIF2 phosphorylation. Zeenko VV, Wang C, Majumder M, Komar AA, Snider MD, Merrick WC, Kaufman RJ, Hatzoglou M. RNA 14 593-602 (2008)
  6. Genome scale evolution of myxoma virus reveals host-pathogen adaptation and rapid geographic spread. Kerr PJ, Rogers MB, Fitch A, Depasse JV, Cattadori IM, Twaddle AC, Hudson PJ, Tscharke DC, Read AF, Holmes EC, Ghedin E. J Virol 87 12900-12915 (2013)
  7. Myxoma virus infection of primary human fibroblasts varies with cellular age and is regulated by host interferon responses. Johnston JB, Nazarian SH, Natale R, McFadden G. Virology 332 235-248 (2005)
  8. Comparative analysis of the complete genome sequence of the California MSW strain of myxoma virus reveals potential host adaptations. Kerr PJ, Rogers MB, Fitch A, Depasse JV, Cattadori IM, Hudson PJ, Tscharke DC, Holmes EC, Ghedin E. J Virol 87 12080-12089 (2013)
  9. Genome sequence of SG33 strain and recombination between wild-type and vaccine myxoma viruses. Camus-Bouclainville C, Gretillat M, Py R, Gelfi J, Guérin JL, Bertagnoli S. Emerg Infect Dis 17 633-638 (2011)
  10. Punctuated Evolution of Myxoma Virus: Rapid and Disjunct Evolution of a Recent Viral Lineage in Australia. Kerr PJ, Eden JS, Di Giallonardo F, Peacock D, Liu J, Strive T, Read AF, Holmes EC. J Virol 93 e01994-18 (2019)
  11. Maladaptation after a virus host switch leads to increased activation of the pro-inflammatory NF-κB pathway. Yu H, Peng C, Zhang C, Stoian AMM, Tazi L, Brennan G, Rothenburg S. Proc Natl Acad Sci U S A 119 e2115354119 (2022)
  12. Reverse Engineering Field Isolates of Myxoma Virus Demonstrates that Some Gene Disruptions or Losses of Function Do Not Explain Virulence Changes Observed in the Field. Liu J, Cattadori IM, Sim DG, Eden JS, Holmes EC, Read AF, Kerr PJ. J Virol 91 e01289-17 (2017)
  13. A highly efficient human cell-free translation system. Aleksashin NA, Chang ST, Cate JHD. RNA 29 1960-1972 (2023)
  14. Genetic Variability of Myxoma Virus Genomes. Braun C, Thürmer A, Daniel R, Schultz AK, Bulla I, Schirrmeier H, Mayer D, Neubert A, Czerny CP. J Virol 91 e01570-16 (2017)
  15. Myxoma virus lacking the host range determinant M062 stimulates cGAS-dependent type 1 interferon response and unique transcriptomic changes in human monocytes/macrophages. Conrad SJ, Raza T, Peterson EA, Liem J, Connor R, Nounamo B, Cannon M, Liu J. PLoS Pathog 18 e1010316 (2022)
  16. Congress Conference report--structural genomics: parsing the architecture of proteins highlights of the ABRF 2004--integrating technologies in proteomics and genomics, February 28-March 2, 2004; Portland, Oregon. Mariani SM. MedGenMed 6 22 (2004)
  17. article-commentary Evolutionary clash between myxoma virus and rabbit PKR in Australia. Burgess HM, Mohr I. Proc Natl Acad Sci U S A 113 3912-3914 (2016)


Related citations provided by authors (1)

  1. An NMR approach to structural proteomics.. Yee A, Chang X, Pineda-Lucena A, Wu B, Semesi A, Le B, Ramelot T, Lee GM, Bhattacharyya S, Gutierrez P, Denisov A, Lee CH, Cort JR, Kozlov G, Liao J, Finak G, Chen L, Wishart D, Lee W, McIntosh LP, Gehring K, Kennedy MA, Edwards AM, Arrowsmith CH Proc Natl Acad Sci U S A 99 1825-30 (2002)

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