Stepwise activation of the pro-apoptotic protein Bid at mitochondrial membranes

Apoptosis regulation at the mitochondria membrane level

“…At the MOM, Bid undergoes conformational changes in a stepwise manner from a compact structure to a more elongated conformation to induce Bax activation. A recent study utilizing spin-label ESR and site-directed PEGylation shows at this stage, tBid undergoes a significant rearrangement of its α6-α8 helices when in contact with the MOM, increasing accessibility of its BH3 domain α3 helix but maintaining overall structural integrity [58]. This is proposed to be a vital step in its interaction with Bax.…”

Structural insights into apoptotic regulation of human Bfk as a novel Bcl-2 family member

“…In this regard, tBfk that lacks a transmembrane region but shares a similar motif in the helix α5 with tBid might also adopt its helix α5-α6 region for a subcellular localization and association with a membrane. Therefore, we suggest that Bfk and Bid have the same mechanism underlying the formation of the truncated conformation and association with MOM, in which tBid dissociates from helices α1-α1′ upon caspase cleavage and contact with mitochondrial membranes [49] , [50] , [51] and its exposed helix α5 embeds into mitochondrial outer membranes [13] , [17] , [18] . However, the cellular localization of tBfk has not yet been identified and the cell-based evidence for the unfolding of tBfk in the presence of a membrane to elicit a pro-apoptotic signal remains lacking.…”

“…In contrast to multi-domain Bcl-2 family proteins, pro-apoptotic BH3-only proteins are intrinsically disordered and, except for Bid, exhibit pro-apoptotic activity without forming the Bcl-2 fold [12] . Bid is a BH3-only protein known to induce the activation of pro-apoptotic pore-formers [11] , [13] , although it remains debated whether the direct binding of BH3-only proteins to Bax/Bak is essential to Bax/Bak activation or whether they play an indirect role in the activation by neutralizing only anti-apoptotic Bcl-2 proteins, such as Bcl-X L or Mcl-1 [14] . Full-length Bid maintains the Bcl-2 fold in the cytosol until it is cleaved by caspases [15] , [16] .…”

Protein Stability Depends Critically on the Surface Hydrogen-Bonding Network: A Case Study of Bid Protein

“…The BH3 interacting-domain death agonist (Bid) protein, a proapoptotic member of the BCL2 protein family with an approximate molecular weight of 22 kDa (195 aa; Figure S1A), was previously identified to be highly resistant against thermal and chemical denaturation and is used as a model protein in the present study. − Here, we report for the first time, cold denaturation of the Bid protein. We show how the cold denaturation of Bid can be induced/inhibited by changes in the concentrations of denaturants, including guanidine hydrochloride (GdnHCl) and urea, together with glycerol that modulates the strength of protein internal and surface interactions.…”