tBID, a membrane-targeted death ligand, oligomerizes BAK to release cytochrome c
摘要：
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.
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关键词：
Animals Mice Cell Membrane Biopolymers Cytochrome c Group Membrane Proteins Allosteric Regulation bcl-2 Homologous Antagonist-Killer Protein Carrier Proteins BH3 Interacting Domain Death Agonist Protein
DOI：
10.1101/gad.14.16.2060
被引量：
年份：
2000
BMJ
Wiley
万方医学
掌桥科研
NCBI
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