ISSN:
0948-5023
Keywords:
Keywords Structure prediction
;
Apoptosis
;
Proto-oncogene proteins
;
G-proteins
;
Caspase
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s008940050134
Permalink
