| First Author | Wei MC | Year | 2000 |
| Journal | Genes Dev | Volume | 14 |
| Issue | 16 | Pages | 2060-71 |
| PubMed ID | 10950869 | Mgi Jnum | J:172906 |
| Mgi Id | MGI:5009197 | Doi | 10.1101/gad.14.16.2060 |
| Citation | Wei MC, et al. (2000) tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c. Genes Dev 14(16):2060-71 |
| abstractText | TNFR1/Fas engagement results in the cleavage of cytosolic BID to truncated tBID, which translocates to mitochondria. Immunodepletion and gene disruption indicate BID is required for cytochrome c release. Surprisingly, the three-dimensional structure of this BH3 domain-only molecule revealed two hydrophobic alpha-helices suggesting tBID itself might be a pore-forming protein. Instead, we demonstrate that tBID functions as a membrane-targeted death ligand in which an intact BH3 domain is required for cytochrome c release, but not for targeting. Bak-deficient mitochondria and blocking antibodies reveal tBID binds to its mitochondrial partner BAK to release cytochrome c, a process independent of permeability transition. Activated tBID results in an allosteric activation of BAK, inducing its intramembranous oligomerization into a proposed pore for cytochrome c efflux, integrating the pathway from death receptors to cell demise. |
