6L8V

membrane-bound Bax helix2-helix5 domain

Summary for 6L8V

• Entry DOI: 10.2210/pdb6l8v/pdb
• NMR Information: BMRB: 36294
• Descriptor: Apoptosis regulator BAX (1 entity in total)
• Functional Keywords: bax, membrane-bound, stability, core-domain, dimer, apoptosis
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 2
• Total formula weight: 17980.53

Authors

OuYang, B.,Lv, F. (deposition date: 2019-11-07, release date: 2020-11-11, Last modification date: 2024-05-15)

Primary citation

Lv, F.,Qi, F.,Zhang, Z.,Wen, M.,Kale, J.,Piai, A.,Du, L.,Wang, S.,Zhou, L.,Yang, Y.,Wu, B.,Liu, Z.,Del Rosario, J.,Pogmore, J.,Chou, J.J.,Andrews, D.W.,Lin, J.,OuYang, B.
An amphipathic Bax core dimer forms part of the apoptotic pore wall in the mitochondrial membrane.
Embo J., 40:e106438-e106438, 2021

PubMed Abstract: 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.

PubMed: 34101209
DOI: 10.15252/embj.2020106438

Experimental method

SOLUTION NMR