PMID- 10228148 OWN - NLM STAT- MEDLINE DCOM- 19990628 LR - 20220318 IS - 0261-4189 (Print) IS - 0261-4189 (Linking) VI - 18 IP - 9 DP - 1999 May 4 TI - Conformation of the Bax C-terminus regulates subcellular location and cell death. PG - 2330-41 AB - Bax, a pro-apoptotic member of the Bcl-2 family, translocates from the cytosol to the mitochondria during programmed cell death. We report here that both gain-of-function and loss-of-function mutations can be achieved by altering a single amino acid in the Bax hydrophobic C-terminus. The properly mutated C-terminus of Bax can target a non-relevant protein to the mitochondria, showing that specific conformations of this domain alone allow mitochondrial docking. These data along with N-terminus epitope exposure experiments suggest that the C- and the N-termini interact and that upon triggering of apoptosis, Bax changes conformation, exposing these two domains to insert into the mitochondria and regulate the cell death machinery. FAU - Nechushtan, A AU - Nechushtan A AD - Biochemistry Section, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. FAU - Smith, C L AU - Smith CL FAU - Hsu, Y T AU - Hsu YT FAU - Youle, R J AU - Youle RJ LA - eng PT - Journal Article PL - England TA - EMBO J JT - The EMBO journal JID - 8208664 RN - 0 (BAX protein, human) RN - 0 (BCL2L1 protein, human) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (bcl-2-Associated X Protein) RN - 0 (bcl-X Protein) SB - IM MH - Amino Acid Sequence MH - *Apoptosis MH - Biological Transport MH - Cell Compartmentation MH - Cytoplasm/*metabolism MH - Humans MH - Mitochondria/*metabolism MH - Molecular Sequence Data MH - Mutation MH - Protein Conformation MH - Proto-Oncogene Proteins/chemistry/genetics/*metabolism MH - Proto-Oncogene Proteins c-bcl-2/metabolism MH - Sequence Deletion MH - bcl-2-Associated X Protein MH - bcl-X Protein PMC - PMC1171316 EDAT- 1999/05/06 00:00 MHDA- 1999/05/06 00:01 CRDT- 1999/05/06 00:00 PHST- 1999/05/06 00:00 [pubmed] PHST- 1999/05/06 00:01 [medline] PHST- 1999/05/06 00:00 [entrez] AID - 10.1093/emboj/18.9.2330 [doi] PST - ppublish SO - EMBO J. 1999 May 4;18(9):2330-41. doi: 10.1093/emboj/18.9.2330.