The role of cardiolipin in promoting the membrane pore-forming activity of BAX oligomers.

BCL-2-associated X (BAX) protein acts as a gatekeeper in regulating mitochondria-dependent apoptosis. Under cellular stress, BAX becomes activated and transforms into a lethal oligomer that causes mitochondrial outer membrane permeabilization (MOMP). Previous studies have identified several structural features of the membrane-associated BAX oligomer; they include the formation of the BH3-in-groove dimer, the collapse of the helical hairpin α5-α6, and the membrane insertion of α9 helix.

Oligomerization process of Bcl-2 associated X protein revealed from intermediate structures in solution.

Upon apoptotic stress, Bcl-2 associated X (BAX) protein undergoes conformational changes and oligomerizes, leading to the mitochondrial membrane permeabilization and cell death. While structures of the resultant oligomer have been extensively studied, little is known about the intermediates that describe the reaction pathway from the inactive monomers to activated oligomers. Here we characterize the intermediate structures of BAX using combined small-angle X-ray scattering (SAXS) with on-line gel-filtration and electron spin resonance (ESR).

Evidence for an Induced-Fit Process Underlying the Activation of Apoptotic BAX by an Intrinsically Disordered BimBH3 Peptide.

Apoptotic BAX protein functions as a critical gateway to mitochondria-mediated apoptosis. A diversity of stimuli has been implicated in initiating BAX activation, but the triggering mechanism remains elusive. Here we study the interaction of BAX with an intrinsically disordered BH3 motif of Bim protein (BimBH3) using ESR techniques.

BAX-induced apoptosis can be initiated through a conformational selection mechanism.

BAX protein plays a key role in the mitochondria-mediated apoptosis. However, it remains unclear by what mechanism BAX is triggered to initiate apoptosis. Here, we reveal the mechanism using electron spin resonance (ESR) techniques.

Kinetics study on the HIV-1 ectodomain protein quaternary structure formation reveals coupling of chain folding and self-assembly in the refolding cascade.

Entry of HIV-1 into the target cell is mediated by the envelope glycoprotein consisting of noncovalently associated surface subunit gp120 and transmembrane subunit gp41. To form a functional gp41 complex, the protein undergoes hairpin formation and self-assembly. The fusion event can be inhibited by gp41-derived peptides at nanomolar concentration and is highly dependent on the time of addition, implying a role of folding kinetics on the inhibitory action.

Identification of complex dynamic modes on prion protein peptides using multifrequency ESR with mesoporous materials.

Identifying protein dynamics is essential for studying protein function. However, the time-scale of dynamic modes varies over domains and segments of a protein. Here we describe an approach using multifrequency ESR with mesoporous materials for protein dynamics in confined nanospace that may mimic the crowded nature within a cell where proteins evolve to fold.