BH 3‐in‐groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes
| Autor: | Alessandro Senes, Feng He, Xuejun C. Zhang, Justin Kale, Jingzhen Ding, Suzanne M. Lapolla, Samson G.F. Condon, Bo Huang, Zhi Zhang, Jianing Li, Sabareesh Subramaniam, David W. Andrews, Franklin A. Hays, Jialing Lin, Hetal Brahmbhatt, Chenyi Liao |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Dimer Apoptosis Mitochondrion Biology General Biochemistry Genetics and Molecular Biology Cell Line 03 medical and health sciences chemistry.chemical_compound Animals Immunoprecipitation Molecular Biology bcl-2-Associated X Protein Mitochondrial outer membrane permeabilization General Immunology and Microbiology General Neuroscience Articles Cell biology Mutational analysis bcl-2 Homologous Antagonist-Killer Protein 030104 developmental biology Membrane chemistry Mitochondrial Membranes Helix Biophysics Dimerization Groove (joinery) Chemical labeling Protein Binding |
| Zdroj: | The EMBO Journal. 35:208-236 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.15252/embj.201591552 |
| Popis: | Pro‐apoptotic Bax induces mitochondrial outer membrane permeabilization (MOMP) by forming oligomers through a largely undefined process. Using site‐specific disulfide crosslinking, compartment‐specific chemical labeling, and mutational analysis, we found that activated integral membrane Bax proteins form a BH3‐in‐groove dimer interface on the MOM surface similar to that observed in crystals. However, after the α5 helix was released into the MOM, the remaining interface with α2, α3, and α4 helices was rearranged. Another dimer interface was formed inside the MOM by two intersected or parallel α9 helices. Combinations of these interfaces generated oligomers in the MOM. Oligomerization was initiated by BH3‐in‐groove dimerization, without which neither the other dimerizations nor MOMP occurred. In contrast, α9 dimerization occurred downstream and was required for release of large but not small proteins from mitochondria. Moreover, the release of large proteins was facilitated by α9 insertion into the MOM and localization to the pore rim. Therefore, the BH3‐in‐groove dimerization on the MOM nucleates the assembly of an oligomeric Bax pore that is enlarged by α9 dimerization at the rim. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text