Helix 6 of tBid is necessary but not sufficient for mitochondrial binding activity

X. Hu, Z. Han, J. H. Wyche, E. A. Hendrickson

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The apoptosis effector Bid regulates cell death at the level of mitochondrial cytochrome c efflux. Bid consists of 8 α-helices (designated H1 through H8, respectively) and is a soluble cytosolic protein in its native state. Proteolysis of the N-terminus (encompassing H1 and H2) of Bid yields activated "tBid" (truncated Bid), which translocates to the mitochondria and induces the efflux of cytochrome c. Here, we demonstrate that helix H6 of tBid is necessary, albeit not sufficient, for mitochondrial binding. In particular, a 33 amino acid long domain, which encompassed H6 and H7, behaved as the minimum domain in tBid that was sufficient for mitochondrial binding. Unexpectedly, the hydrophobic surface of these helices could be mutated without altering the binding activity of the domain, implying that the secondary structure of the helices may be the key determinant of binding. These experiments expand our mechanistic understanding of the apoptotic regulator, tBid.

Original languageEnglish (US)
Pages (from-to)277-289
Number of pages13
JournalApoptosis
Volume8
Issue number3
DOIs
StatePublished - Jun 1 2003

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Cytochromes c
Proteolysis
Mitochondria
Cell death
Cell Death
Apoptosis
Amino Acids
Proteins
Experiments

Keywords

  • Apoptosis
  • BH3 domain
  • Cytochrome c
  • Mitochondria
  • TBid

Cite this

Helix 6 of tBid is necessary but not sufficient for mitochondrial binding activity. / Hu, X.; Han, Z.; Wyche, J. H.; Hendrickson, E. A.

In: Apoptosis, Vol. 8, No. 3, 01.06.2003, p. 277-289.

Research output: Contribution to journalArticle

Hu, X. ; Han, Z. ; Wyche, J. H. ; Hendrickson, E. A. / Helix 6 of tBid is necessary but not sufficient for mitochondrial binding activity. In: Apoptosis. 2003 ; Vol. 8, No. 3. pp. 277-289.
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