Molecular basis of Bcl-XL-p53 interaction: Insights from molecular dynamics simulations

Cited 27 time in scopus
Metadata Downloads
Title
Molecular basis of Bcl-XL-p53 interaction: Insights from molecular dynamics simulations
Author(s)
N Bharatham; Seung-Wook Chi; H S Yoon
Bibliographic Citation
PLoS One, vol. 6, no. 10, pp. e26014-e26014
Publication Year
2011
Abstract
Bcl-XL, an antiapoptotic Bcl-2 family protein, plays a central role in the regulation of the apoptotic pathway. Heterodimerization of the antiapoptotic Bcl-2 family proteins with the proapoptotic family members such as Bad, Bak, Bim and Bid is a crucial step in the apoptotic regulation. In addition to these conventional binding partners, recent evidences reveal that the Bcl-2 family proteins also interact with noncanonical binding partners such as p53. Our previous NMR studies showed that Bcl-XL: BH3 peptide and Bcl-XL: SN15 peptide (a peptide derived from residues S15-N29 of p53) complex structures share similar modes of bindings. To further elucidate the molecular basis of the interactions, here we have employed molecular dynamics simulations coupled with MM/PBSA approach. Bcl-XL and other Bcl-2 family proteins have 4 hydrophobic pockets (p1-p4), which are occupied by four systematically spaced hydrophobic residues (h1-h4) of the proapoptotic Bad and Bak BH3 peptides. We observed that three conserved hydrophobic residues (F19, W23 and L26) of p53 (SN15) peptide anchor into three hydrophobic pockets (p2-p4) of Bcl-XL in a similar manner as BH3 peptide. Our results provide insights into the novel molecular recognition by Bcl-XL with p53.
ISSN
1932-6203
Publisher
Public Library of Science
DOI
http://dx.doi.org/10.1371/journal.pone.0026014
Type
Article
Appears in Collections:
Division of Biomedical Research > 1. Journal Articles
Files in This Item:

Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.