Locating Herpesvirus Bcl-2 Homologs in the Specificity Landscape of Anti-Apoptotic Bcl-2 Proteins
作者： Glenna Wink Foight , Amy E. Keating
DOI: 10.1016/J.JMB.2015.05.015
关键词:
摘要: Viral homologs of the anti-apoptotic Bcl-2 proteins are highly diverged from their mammalian counterparts, yet they perform overlapping functions by binding and inhibiting BH3 (Bcl-2 homology 3)-motif-containing proteins. We investigated properties herpesvirus KSBcl-2, BHRF1, M11, as relate to those human Mcl-1, Bfl-1, Bcl-w, Bcl-xL, Bcl-2. Analysis sequence structure grooves showed that, despite low identity, M11 has structural similarities Bcl-2, Bcl-w. BHRF1 KSBcl-2 more structurally similar Mcl-1 than other Binding BH3-like peptides that specificity a restricted profile; preferences distinct Because herpesviruses associated with malignancies, we screened computationally designed peptide libraries using bacterial surface display identify selective binders or BHRF1. The resulting bound in preference but only modest over Mcl-1. Rational mutagenesis increased against dissociation constant 2.9nM for >1000-fold proteins, well >70-fold In addition providing new insights into viral specificity, this study will inform future work analyzing interaction homologous domains designing specific protein partners.
core.ac.uk
elsevier.com
sci-hub.se 参考文章(79)
Päivi M. Ojala, Kazuhito Yamamoto, Esmeralda Castaños-Vélez, Peter Biberfeld, Stanley J. Korsmeyer, Tomi P. Mäkelä, The apoptotic v-cyclin–CDK6 complex phosphorylates and inactivates Bcl-2 Nature Cell Biology. ,vol. 2, pp. 819- 825 ,(2000) , 10.1038/35041064
J. Marie Hardwick, Cyclin' on the viral path to destruction. Nature Cell Biology. ,vol. 2, ,(2000) , 10.1038/35041126
Shlomit Erlich, Liat Mizrachy, Oshik Segev, Liora Lindenboim, Ofir Zmira, Sheli Adi-Harel, Joel A. Hirsch, Reuven Stein, Ronit Pinkas-Kramarski, Differential interactions between Beclin 1 and Bcl-2 family members. Autophagy. ,vol. 3, pp. 561- 568 ,(2007) , 10.4161/AUTO.4713
A. L. Desbien, J. W. Kappler, P. Marrack, The Epstein-Barr virus Bcl-2 homolog, BHRF1, blocks apoptosis by binding to a limited amount of Bim Proceedings of the National Academy of Sciences of the United States of America. ,vol. 106, pp. 5663- 5668 ,(2009) , 10.1073/PNAS.0901036106
M Kvansakul, H Yang, W D Fairlie, P E Czabotar, S F Fischer, M A Perugini, D C S Huang, P M Colman, Vaccinia virus anti-apoptotic F1L is a novel Bcl-2-like domain-swapped dimer that binds a highly selective subset of BH3-containing death ligands. Cell Death & Differentiation. ,vol. 15, pp. 1564- 1571 ,(2008) , 10.1038/CDD.2008.83
Sophie Pattingre, Amina Tassa, Xueping Qu, Rita Garuti, Xiao Huan Liang, Noboru Mizushima, Milton Packer, Michael D. Schneider, Beth Levine, Bcl-2 Antiapoptotic Proteins Inhibit Beclin 1-Dependent Autophagy Cell. ,vol. 122, pp. 927- 939 ,(2005) , 10.1016/J.CELL.2005.07.002
Glenna Wink Foight, Jeremy A. Ryan, Stefano V. Gullá, Anthony Letai, Amy E. Keating, Designed BH3 Peptides with High Affinity and Specificity for Targeting Mcl-1 in Cells ACS Chemical Biology. ,vol. 9, pp. 1962- 1968 ,(2014) , 10.1021/CB500340W
Anthony Letai, Michael C. Bassik, Loren D. Walensky, Mia D. Sorcinelli, Solly Weiler, Stanley J. Korsmeyer, Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. Cancer Cell. ,vol. 2, pp. 183- 192 ,(2002) , 10.1016/S1535-6108(02)00127-7
J. Marie Hardwick, Ying-bei Chen, Elizabeth A. Jonas, Multipolar functions of BCL-2 proteins link energetics to apoptosis. Trends in Cell Biology. ,vol. 22, pp. 318- 328 ,(2012) , 10.1016/J.TCB.2012.03.005
E. H.- Y. Cheng, J. Nicholas, D. S. Bellows, G. S. Hayward, H.-G. Guo, M. S. Reitz, J. M. Hardwick, A Bcl-2 homolog encoded by Kaposi sarcoma-associated virus, human herpesvirus 8, inhibits apoptosis but does not heterodimerize with Bax or Bak Proceedings of the National Academy of Sciences of the United States of America. ,vol. 94, pp. 690- 694 ,(1997) , 10.1073/PNAS.94.2.690