2m5i

Publication Abstract from PubMed

The Bcl-2 family proteins regulate mitochondria mediated apoptosis through intricate molecular mechanisms. One of the pro-apoptotic proteins, tBid, can induce apoptosis by promoting Bax activation, Bax homo-oligomerization and mitochondrial outer membrane permeabilization. Association of tBid on the mitochondrial outer membrane is key to its biological function. Therefore knowing the conformation of tBid on the membrane will be the first step toward understanding its crucial role in triggering apoptosis. Here, we present the NMR characterization of the structure and dynamics of human tBid in LPPG micelles. Our data showed that tBid is monomeric with six well-defined alpha-helices in the micelles. Compared to the full-length Bid structure, a longer flexible loop between tBid helix alpha4 and alpha5 was observed. Helices in tBid do not pack into a compact fold but form an extended structure with a C-shape configuration in the micelles. All six tBid helices were shown to interact with LPPG micelles, with helix alpha6 and alpha7 being more embedded. Of note, the BH3-containing helix alpha3, which previously believed to be exposed above the membrane surface, is also membrane associated, suggesting an on-the-membrane binding mode for tBid interaction with Bax. Our data provided structural details on membrane-associated state of tBid and the functional implications of its membrane-associated BH3 domain.

Structural insights of tBid, the caspase-8 activated Bid, and its BH3 domain.,Wang Y, Tjandra N J Biol Chem. 2013 Oct 24. PMID:24158446^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.