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Structural Perspectives on BCL-2 Family of Proteins

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Cell Death

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Abstract

BCL-2 proteins are a family of pro- and anti-apoptotic proteins that regulate a critical step in the mitochondrial apoptotic pathway, the permeabilization of the mitochondrial outer membrane. Because apoptosis and mitochondrial function play an important role in physiology and a number of diseases, intensive investigation over the past two decades has been invested to understand in detail the structure and function of the BCL-2 proteins. Structural biology investigations of BCL-2 proteins have provided tremendous insights into our understanding of their structure–function relationships and models have been proposed to explain how the BCL-2 family members form a network of interactions to control apoptosis signaling. Here, we will review the available structural information of pro- and anti-apoptotic members and the structures of their interaction in homodimerization and heterodimerization. We will discuss the structural insights for each structural domain of BCL-2 proteins that determine their function in the cytosol and the outer mitochondrial membrane. Furthermore, we will discuss the structural details of the interactions between BCL-2 family members and the various structural paradigms that ultimately regulate the activation of apoptosis.

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Acknowledgements

I would like to thank my laboratory members, past and present collaborators for stimulating discussions, Dr. Thomas Garner for reviewing this chapter, and grant support by the National Institute of Health, National Heart, Lung and Blood Institute (R00HL095929) and National Cancer Institute (P30CA013330-39S1).

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  1. Department of Biochemistry, Albert Einstein College of Medicine, Forchheimer G46, Bronx, NY, 10461, USA

    Evripidis Gavathiotis Ph.D.

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Correspondence to Evripidis Gavathiotis Ph.D. .

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  1. Dept. of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA

    Hao Wu

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Gavathiotis, E. (2014). Structural Perspectives on BCL-2 Family of Proteins. In: Wu, H. (eds) Cell Death. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9302-0_11

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