Conformational Heterogeneity of Bax Helix 9 Dimer for Apoptotic Pore Formation.

ABSTRACT: Helix α9 of Bax protein can dimerize in the mitochondrial outer membrane (MOM) and lead to apoptotic pores. However, it remains unclear how different conformations of the dimer contribute to the pore formation on the molecular level. Thus we have investigated various conformational states of the α9 dimer in a MOM model - using computer simulations supplemented with site-specific mutagenesis and crosslinking of the α9 helices. Our data not only confirmed the critical membrane environment for the α9 stability and dimerization, but also revealed the distinct lipid-binding preference of the dimer in different conformational states. In our proposed pathway, a crucial iso-parallel dimer that mediates the conformational transition was discovered computationally and validated experimentally. The c

SUBMITTER: Liao C 

PROVIDER: S-EPMC4933972 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature