Grouper iridovirus GIV66 is a Bcl-2 protein that inhibits apoptosis by exclusively sequestering Bim

The Journal of Biological Chemistry
Suresh BanjaraMarc Kvansakul

Abstract

Programmed cell death or apoptosis is a critical mechanism for the controlled removal of damaged or infected cells, and proteins of the Bcl-2 family are important arbiters of this process. Viruses have been shown to encode functional and structural homologs of Bcl-2 to counter premature host-cell apoptosis and ensure viral proliferation or survival. Grouper iridovirus (GIV) is a large DNA virus belonging to the Iridoviridae family and harbors GIV66, a putative Bcl-2-like protein and mitochondrially localized apoptosis inhibitor. However, the molecular and structural basis of GIV66-mediated apoptosis inhibition is currently not understood. To gain insight into GIV66's mechanism of action, we systematically evaluated its ability to bind peptides spanning the BH3 domain of pro-apoptotic Bcl-2 family members. Our results revealed that GIV66 harbors an unusually high level of specificity for pro-apoptotic Bcl-2 and displays affinity only for Bcl-2-like 11 (Bcl2L11 or Bim). Using crystal structures of both apo-GIV66 and GIV66 bound to the BH3 domain from Bim, we unexpectedly found that GIV66 forms dimers via an interface that results in occluded access to the canonical Bcl-2 ligand-binding groove, which breaks apart upon Bim binding....Continue Reading

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Citations

Jun 18, 2019·Acta Crystallographica. Section F, Structural Biology Communications·Thushara Welwelwela HewageMihwa Lee
Jul 17, 2019·Endocrinology·Qian HuangEmrah Altindis
May 16, 2020·The FEBS Journal·Chathura D SuraweeraMarc Kvansakul
Jan 17, 2020·Biomolecules·Suresh BanjaraMarc Kvansakul
Sep 22, 2018·Cell Death & Disease·Chathura D SuraweeraMarc Kvansakul
Nov 12, 2020·The Biochemical Journal·Chathura D SuraweeraMarc Kvansakul
Dec 15, 2020·Biochimica Et Biophysica Acta. Reviews on Cancer·Lin ZhaoYa Cao
Feb 15, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Chaoyue YangYuan Yuan
Dec 31, 2020·Pathogens·Chathura D SuraweeraMarc Kvansakul

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