In:
Journal of Cellular Biochemistry, Wiley, Vol. 99, No. 1 ( 2006-09), p. 305-318
Kurzfassung:
Bax, a multi‐domain protein belonging to the large family of Bcl‐2 proteins, has a pivotal role for the initiation of the cytochrome c ‐mediated apoptosis, a vital physiologic process to eliminate damaged or unwanted cells. In response to specific stimuli Bax translocates from cytosol to mitochondria outer membrane where a process of oligomerization occurs with pore formation through which cytochrome c and other death molecules escape. The pro‐death action of Bax is regulated by the interaction with other pro‐survival proteins. However, the conformational changes and the structural details necessary for homo and hetero interaction with other regulating proteins are largely unknown. This article reports a combined investigation of molecular dynamics (MD) simulation and automated docking that evidence the molecular regions of Bax involved in the binding with anti‐apoptotic exapeptide (Bip) designed from Ku70, a subunit of the protein complex essential for non‐homologous DNA repair but that inhibits also the Bax translocation to mitochondria. Since Bip suppresses apoptosis induced by several anti‐cancer drugs, it appears relevant to achieve a better understanding of the structural and dynamical aspects that characterize the Bip–Bax complex in view of potential therapeutic implications. The present results show that the Bax region with the highest affinity for Bip is located in proximity of BH3 homology domain of Bax and also involves the α‐helices 1 and 8. Moreover, the comparison of essential motions of Bax at 300 and 400 K before and after the formation of the complex with Bip evidences how the binding with the exa‐peptide affects the collective motions of specific molecular districts of Bax considered to have functional relevance. J. Cell. Biochem. © 2006 Wiley‐Liss, Inc.
Materialart:
Online-Ressource
ISSN:
0730-2312
,
1097-4644
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2006
ZDB Id:
1479976-5
SSG:
12
