1. ¹Howard Hughes Medical Institute, Integrated Department of Immunology, Zuckerman Family/Canyon Ranch Crystallography Laboratory, National Jewish Medical and Research Center, Denver, CO, USA
2. ²Integrated Department of Immunology, University of Colorado Health Science Center, Denver, CO, USA
3. ³Department of Biochemistry and Molecular Genetics, University of Colorado Health Science Center, Denver, CO, USA
4. ⁴Department of Pharmacology and Program in Biomolecular Structure, University of Colorado Health Science Center, Denver, CO, USA

Correspondence: JW Kappler, Howard Hughes Medical Institute, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA. Tel: +303 398 1322; Fax: +303 398 1396; E-mail: kapplerj@njc.org

Received 29 May 2006; Revised 13 July 2006; Accepted 14 July 2006; Published online 1 September 2006.

Abstract

The Bcl-2 family member Bax plays a critical role in apoptosis. In healthy resting cells, Bax resides in the cytoplasm and loosely attached to the mitochondrial membrane. Apoptotic stimuli induce Bax activation, which is characterized by translocation and multimerization on the mitochondrial membrane surface resulting in exposure of an amino terminal epitope recognized by the monoclonal antibody 6A7. To understand the structural changes that occur during Bax activation, we determined the crystal structure of a Bax peptide bound to the 6A7 Fab fragment to a resolution of 2.3 Å. The structure reveals the conformation of the 6A7 peptide epitope on Bax in the activated form and elucidates the extensive structural changes that Bax must undergo during the conversion from its native to its activated conformation.