Abstract
Apoptosis (programmed cell death, PCD) is a characteristic type of cell death in which a regulated cellular response pathway mediated by cysteine proteases of the caspase family and Bcl-2 family proteins results in ordered and non-inflammatory involution of the cell. The CED-4 protein and its recently identified mammalian homologue Apaf-1 are critical but functionally uncharacterized components of the cell death machinery. We present here a three-dimensional molecular model for the central domain of CED-4, its alternatively spliced transcript (CED-4l) and Apaf-1. A novel protein family is identified and structure prediction for the family identifies a G-protein-like fold with high reliability. The three-dimensional model provides a potential structural explanation for the alternatively spliced variant as well as the known point mutations in CED-4. Regions of the CED-4 and Apaf-1 sequences which may interact with caspases and the Bcl-2 family are proposed. This new information provides a structural molecular framework for the interaction of CED-4-like proteins with the caspases and the Bcl-2 family in the regulation of apoptosis which is analogous to G-protein mediated interactions in well-defined signal transduction pathways.
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Received: 22 October 1997 / Accepted: 28 January 1998 / Published: 17 February 1998
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Cardozo, T., Abagyan, R. Molecular Modeling of the Domain Shared Between CED-4 and its Mammalian Homologue Apaf-1: A Structural Relationship to the G-proteins. J Mol Med 4, 83–93 (1998). https://doi.org/10.1007/s008940050134
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DOI: https://doi.org/10.1007/s008940050134