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An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial␣membrane
Author(s) -
Lv Fujiao,
Qi Fei,
Zhang Zhi,
Wen Maorong,
Kale Justin,
Piai Alessandro,
Du Lingyu,
Wang Shuqing,
Zhou Liujuan,
Yang Yaqing,
Wu Bin,
Liu Zhijun,
Rosario Juan,
Pogmore Justin,
Chou James J,
Andrews David W,
Lin Jialing,
OuYang Bo
Publication year - 2021
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020106438
Subject(s) - lipid bilayer , dimer , biophysics , bilayer , biology , cytosol , inner mitochondrial membrane , mitochondrion , amphiphile , membrane , biochemistry , microbiology and biotechnology , crystallography , chemistry , enzyme , organic chemistry , copolymer , polymer
Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding in the cytosolic leaflet of the lipid bilayer, thus generating tension to induce a lipid pore with radially arranged lipids forming the wall. Alternatively, Bax proteins might comprise part of the pore wall. However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determined a high‐resolution structure of the Bax core region, revealing a dimer with the nonpolar surface covering the lipid bilayer edge and the polar surface exposed to water. The dimer tilts from the bilayer normal, not only maximizing nonpolar interactions with lipid tails but also creating polar interactions between charged residues and lipid heads. Structure‐guided mutations demonstrate the importance of both types of protein–lipid interactions in Bax pore assembly and core dimer configuration. Therefore, the Bax core dimer forms part of the proteolipid pore wall to permeabilize mitochondria.