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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
9
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pubmed:dateCreated |
2003-8-22
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pubmed:abstractText |
Because of structural homology with the transmembrane domain of Bcl-2, the proapoptotic protein Bax has been proposed to be anchored to the outer membrane of mitochondria through its carboxy-terminal end (CT). We took advantage of the absence of Bcl-2 family members in yeast to further investigate the role of Bax CT in its mitochondrial association and function. The complete deletion or the addition of a C-terminal c-myc tag as well as the replacement of CT by a random coiled sequence enhanced membrane insertion of Bax. It has previously been suggested that conformational change in the N-terminal end of Bax would allow the C-terminal end to play its anchoring function. We found that a mutant truncated in both N- and C-termini still exhibited a strong binding activity to mitochondria. In mammals, Bax interaction with the caspase-8-generated truncated form of Bid (tc-Bid) is believed to promote a conformational change necessary for the insertion of Bax into mitochondria. We coexpressed Bax and tc-Bid in yeast and found that native Bax functions are not stimulated by tc-Bid, whereas functions of an active variant with a modified CT are. We propose that Bax CT has to undergo a conformational change to allow the insertion of Bax in mitochondria but, contrary to current views, is not a bona fide membrane anchor.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1350-9047
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1068-77
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12934081-Amino Acid Sequence,
pubmed-meshheading:12934081-Animals,
pubmed-meshheading:12934081-BH3 Interacting Domain Death Agonist Protein,
pubmed-meshheading:12934081-Carrier Proteins,
pubmed-meshheading:12934081-Cell Death,
pubmed-meshheading:12934081-Mitochondria,
pubmed-meshheading:12934081-Mitochondrial Proteins,
pubmed-meshheading:12934081-Molecular Sequence Data,
pubmed-meshheading:12934081-Protein Conformation,
pubmed-meshheading:12934081-Proto-Oncogene Proteins,
pubmed-meshheading:12934081-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:12934081-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:12934081-Recombinant Fusion Proteins,
pubmed-meshheading:12934081-Sequence Deletion,
pubmed-meshheading:12934081-Sequence Homology, Amino Acid,
pubmed-meshheading:12934081-Yeasts,
pubmed-meshheading:12934081-bcl-2-Associated X Protein
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pubmed:year |
2003
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pubmed:articleTitle |
Investigation of the role of the C-terminus of Bax and of tc-Bid on Bax interaction with yeast mitochondria.
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pubmed:affiliation |
UMR 5095 CNRS/Université de Bordeaux 2, 1 Rue Camille Saint-Saëns, F-33077 Bordeaux, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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