In:
The Journal of Immunology, The American Association of Immunologists, Vol. 178, No. 1_Supplement ( 2007-04-01), p. S117-S117
Abstract:
Apoptosis is essential for lymphocyte development and the maintenance of cellular homeostasis. Previously, we showed that the apoptotic protein, BAX, is a critical mediator of IL-7-withdrawal induced death; yet, how this deadly protein is activated is poorly understood. Under apoptotic stress, BAX translocates to mitochondria, causing cell death. To explain this transitional behavior, we tested the hypothesis that the C-terminal α9 helix of BAX is essential for mitochondrial membrane binding. Using a multi-disciplinary approach, we demonstrated that the lysine at position 189, near the end of the α9 helix, is required for membrane association. Hence, the α9 helix could function as a membrane anchor. However, computational docking analysis revealed a new function for the α9 helix. By binding in reverse orientation to the internal hydrophobic grooves of adjacent BAX molecules, this helix enables dimerization and the release of additional membrane-spanning domains. This reverse orientation of binding places the lysine at position 189 in binding proximity to conserved acidic residues in the BH3 domain of BAX, enabling the interaction between the α9 helix and the pocket. We have, therefore, identified a novel and indispensable role for the C-terminal α9 helix of BAX, demonstrating that, by binding in trans to a hydrophobic groove, this domain unleashes the protein’s lethal activity.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.178.Supp.84.10
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2007
detail.hit.zdb_id:
1475085-5
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