Skip NavigationSkip to Content
Return Return to Search Results

Homogeneous Oligomers of Pro-apoptotic BAX Reveal Structural Determinants of Mitochondrial Membrane Permeabilization

  1. Author:
    Hauseman, Zachary J
    Harvey, Edward P
    Newman, Catherine E
    Wales, Thomas E
    Bucci, Joel C
    Mintseris, Julian
    Schweppe, Devin K
    David, Liron
    Fan,Lixin
    Cohen, Daniel T
    Herce, Henry D
    Mourtada, Rida
    Ben-Nun, Yael
    Bloch, Noah B
    Hansen, Scott B
    Wu, Hao
    Gygi, Steven P
    Engen, John R
    Walensky, Loren D

  2. Author Address

    Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA., Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA., Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA., Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Program in Cellular and Molecular Medicine, Boston Children 39;s Hospital, Boston, MA 02115, USA., Small Angle X-ray Scattering Core, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., The Scripps Research Institute-Florida, Jupiter, FL 33458, USA., Department of Pediatric Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA; Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA. Electronic address: loren_walensky@dfci.harvard.edu.,
    1. Year: 2020
    2. Date: JUL 2
    3. Epub Date: 2020 06 09
  2. Journal: Molecular cell
    1. 79
    2. 1
    3. Pages: 68-+
  4. Type of Article: Article
  5. ISSN: 1097-2765
  1. Abstract:

    BAX is a pro-apoptotic protein that transforms from a cytosolic monomer into a toxic oligomer that permeabilizes the mitochondrial outer membrane. How BAX monomers assemble into a higher-order conformation, and the structural determinants essential to membrane permeabilization, remain a mechanistic mystery. A key hurdle has been the inability to generate a homogeneous BAX oligomer (BAXO) for analysis. Here, we report the production and characterization of a full-length BAXO that recapitulates physiologic BAX activation. Multidisciplinary studies revealed striking conformational consequences of oligomerization and insight into the macromolecular structure of oligomeric BAX. Importantly, BAXO enabled the assignment of specific roles to particular residues and a helices that mediate individual steps of the BAX activation pathway, including unexpected functionalities of BAX a6 and a9 in driving membrane disruption. Our results provide the first glimpse of a full-length and functional BAXO, revealing structural requirements for the elusive execution phase of mitochondrial apoptosis. Copyright © 2020 Elsevier Inc. All rights reserved.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1016/j.molcel.2020.05.029
  3. PMID: 32533918
  4. View record in Web of Science®
  5. WOS: 000548786000008
  6. PII : S1097-2765(20)30349-X

Library Notes

  1. Fiscal Year: FY2019-2020
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel