Structural studies of Bcl-2-family regulators of apoptosis
- Argonne National Lab., IL (United States). Center for Mechanistic Biology and Biotechnology
The Bcl-2 family of proteins includes about a dozen different proteins which share two small regions of amino acid homology but otherwise exhibit rather modest sequence similarities. The members of this family function as molecular regulators of apoptosis, some as accelerators of cell death and others as inhibitors of apoptosis. The authors analyzed the predicted secondary structures of Bcl-2-family proteins and found that a series of four amphipathic helices, three short {beta}-strands, and a carboxyl-terminal transmembrane helix were conserved throughout the family. Since the Bcl-2-family proteins do not have homology with any proteins of known three-dimensional structure, it seems likely that the tertiary structure assumed by these conserved Bcl-2-family structural elements will represent a completely new protein fold. The authors have prepared recombinant versions of particular proteins of the Bcl-2-family so that the can analyze their molecular structures experimentally. In addition, since some of the Bcl-2-family members homodimerize, they are using small-zone size-exclusion chromatography to analyze the homodimerization of individual, purified Bcl-2-family proteins in order to determine the association and rate constants for these dimerization reactions using computer-simulation methods previously developed in the group. Since certain of these proteins also interest with each other to form heterodimers, the authors also hope to extend the analyses to similarly analyze the heterodimerization of pairs of purified Bcl-2-family proteins.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States)
- DOE Contract Number:
- W-31109-ENG-38
- OSTI ID:
- 251305
- Report Number(s):
- ANL/CMB/CP-90102; CONF-9604136-22; ON: DE96011125; TRN: AHC29614%%33
- Resource Relation:
- Conference: 2. Argonne National Laboratory technical women`s symposium, Argonne, IL (United States), 29-30 Apr 1996; Other Information: PBD: [1996]
- Country of Publication:
- United States
- Language:
- English
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