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PMID:15131699

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Citation

Jeong, SY, Gaume, B, Lee, YJ, Hsu, YT, Ryu, SW, Yoon, SH and Youle, RJ (2004) Bcl-x(L) sequesters its C-terminal membrane anchor in soluble, cytosolic homodimers. EMBO J. 23:2146-55

Abstract

Bcl-x(L) is a potent inhibitor of apoptosis. While Bcl-x(L) can be bound to mitochondria, a substantial fraction, depending on the cell type or tissue, is found in the cytosol of healthy cells. Gel filtration and crosslinking experiments reveal that, unlike monomeric Bax, Bcl-x(L) migrates in a complex of approximately 50 kDa in the cytosol. Co-immunoprecipitation experiments indicate that Bcl-x(L) in the cytosol forms homodimers. The C-terminal hydrophobic tails of two Bcl-x(L) molecules are involved in homodimer formation, and analysis of mutants demonstrates that the C-terminal lysine residue and the G138 residue lining the BH3-binding pocket are required for homodimerization. The flexible loop preceding the C-terminal tail in Bcl-x(L) is longer than that of several monomeric Bcl-2 family members and is a requisite for the homodimer formation. Bad binding to Bcl-x(L) dissociates the homodimers and triggers Bcl-x(L) binding to mitochondrial membranes. The C-terminal tail of Bcl-x(L) is also required to mediate Bcl-x(L)/Bax heterodimer formation. Both mitochondrial import and antiapoptotic activity of different Bcl-x(L) mutants correlate with their ability to form homodimers.

Links

PubMed PMC424420 Online version:10.1038/sj.emboj.7600225

Keywords

Amino Acid Sequence; Animals; Apoptosis/physiology; Binding Sites; Carrier Proteins/metabolism; Cell Line; Cytoplasm/metabolism; Dimerization; Humans; Mitochondria/metabolism; Molecular Sequence Data; Mutation; Peptide Fragments/genetics; Peptide Fragments/metabolism; Protein Binding; Protein Structure, Quaternary; Protein Structure, Secondary; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2/chemistry; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Sequence Alignment; bcl-2-Associated X Protein; bcl-Associated Death Protein; bcl-X Protein

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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