Stephanie C. Fennell

Walter and Eliza Hall Institute of Medical Research

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Ruth M. Kluck

Walter and Eliza Hall Institute of Medical Research

Grant Dewson

University of Melbourne

Amber E. Alsop

Walter and Eliza Hall Institute of Medical Research

Colin Hockings

University of Melbourne

Khatira Anwari

Walter and Eliza Hall Institute of Medical Research

Tobias Kratina

University of Melbourne

Erinna F. Lee

La Trobe University

Ray C. Bartolo

Universidad de Costa Rica

Michael T. Ryan

Monash University

Michael Lazarou

Australian Regenerative Medicine Institute

Cooperative Institutions

Walter and Eliza Hall Institute of Medical Research

University of Melbourne

Monash University

La Trobe University

Peter MacCallum Cancer Centre

Murdoch Children's Research Institute

University of Otago

Olivia Newton-John Cancer Wellness & Research Centre

Weatherford College

Institute for Molecular Science

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Assembly of the Bak Apoptotic Pore

Journal of Biological Chemistry (2013)

Stephen Ma Colin Hockings Khatira Anwari Tobias Kratina Stephanie C. Fennell

10.1074/jbc.m113.490094

Cite

Citations (70)

Dissociation of Bak α1 helix from the core and latch domains is required for apoptosis

Nature Communications (2015)

Amber E. Alsop Stephanie C. Fennell Ray C. Bartolo Iris K. L. Tan Grant Dewson

During apoptosis, Bak permeabilizes mitochondria after undergoing major conformational changes, including poorly defined N-terminal changes. Here, we characterize those changes using 11 antibodies that were epitope mapped using peptide arrays and mutagenesis. After Bak activation by Bid, epitopes throughout the α1 helix are exposed indicating complete dissociation of α1 from α2 in the core and from α6–α8 in the latch. Moreover, disulfide tethering of α1 to α2 or α6 blocks cytochrome c release, suggesting that α1 dissociation is required for further conformational changes during apoptosis. Assaying epitope exposure when α1 is tethered shows that Bid triggers α2 movement, followed by α1 dissociation. However, α2 reaches its final position only after α1 dissociates from the latch. Thus, α1 dissociation is a key step in unfolding Bak into three major components, the N terminus, the core (α2–α5) and the latch (α6–α8). During apoptosis, Bak undergoes major conformational changes that lead to mitochondrial permeabilization. Here, the authors characterize changes that occur within the Bak N-terminus using a series of antibodies and a novel tethering approach, demonstrating that dissociation of the α1 helix is a key early step in the unfolding of Bak.

Helix (gastropod)

10.1038/ncomms7841

Cite

Citations (54)

Mcl-1 and Bcl-xL sequestration of Bak confers differential resistance to BH3-only proteins

Cell Death and Differentiation (2018)

Colin Hockings Amber E. Alsop Stephanie C. Fennell Erinna F. Lee W. Douglas Fairlie

Bcl-xL

Bcl-2 Family

Mode of Action

10.1038/s41418-017-0010-6

Cite

Citations (55)