Conformational changes in BID, a pro-apoptotic BCL-2 family member, upon membrane binding: A site-directed spin labeling study

Joon Oh Kyoung, Scott Barbuto, Natalie Meyer, Ryung Suk Kim, M. John Collier, Stanley J. Korsmeyer

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

The BCL-2 family proteins constitute a critical control point in apoptosis. BCL-2 family proteins display structural homology to channel-forming bacterial toxins, such as colicins, transmembrane domain of diphtheria toxin, and the N-terminal domain of δ-endotoxin. By analogy, it has been hypothesized the BCL-2 family proteins would unfold and insert into the lipid bilayer upon membrane association. We applied the site-directed spin labeling method of electron paramagnetic resonance spectroscopy to the pro-apoptotic member BID. Here we show that helices 6-8 maintain an α-helical conformation in membranes with a lipid composition resembling mitochondrial outer membrane contact sites. However, unlike colicins and the transmembrane domain of diphtheria toxin, these helices of BID are bound to the lipid bilayer without adopting a transmembrane orientation. Our study presents a more detailed model for the reorganization of the structure of tBID on membranes.

Original languageEnglish (US)
Pages (from-to)753-767
Number of pages15
JournalJournal of Biological Chemistry
Volume280
Issue number1
DOIs
StatePublished - Jan 7 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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