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Bid: a Bax-like BH3 protein

Oncogene volume 27, pages S93–S104 (2008)Cite this article

Abstract

Bid, a pro-apoptotic member of the Bcl-2 family, was initially discovered through binding to both pro-apoptotic Bax and anti-apoptotic Bcl-2. During apoptosis, Bid can be cleaved not only by caspase-8 during death receptor apoptotic signaling, but also by other caspases, granzyme B, calpains and cathepsins. Protease-cleaved Bid migrates to mitochondria where it induces permeabilization of the outer mitochondrial membrane that is dependent on the pro-apoptotic proteins Bax and/or Bak, and thus Bid acts as a sentinel for protease-mediated death signals. Although sequence analysis suggests that Bid belongs to the BH3-only subgroup of the Bcl-2 family, structural and phylogenetic analysis suggests that Bid may be more related to multi-BH region proteins such as pro-apoptotic Bax. Analysis of membrane binding by protease-cleaved Bid reveals mechanistic similarities with the membrane binding of Bax. For both proteins, membrane binding is characterized by relief of N-terminal inhibition of sequences promoting migration to membranes, insertion into the bilayer of the central hydrophobic hairpin helices and exposure of the BH3 region. These findings implicate Bid as a BH3-only protein that is both structurally and functionally related to multi-BH region Bcl-2 family proteins such as Bax.

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Acknowledgements

The work in the author's laboratory was supported by grant FRN12517 from the Canadian Institute of Health Research (CIHR), a Tier I Canada Research Chair in Membrane Biogenesis to DWA and a CIHR Canada Graduate Scholarship to LPB.

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  1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada

    L P Billen, A Shamas-Din & D W Andrews

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Billen, L., Shamas-Din, A. & Andrews, D. Bid: a Bax-like BH3 protein. Oncogene 27 (Suppl 1), S93–S104 (2008). https://doi.org/10.1038/onc.2009.47

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