Please use this identifier to cite or link to this item:
|Title:||Dynamics of Bcl-xL in Water and Membrane: Molecular Simulations||Authors:||Maity, A.
Ghosh Dastidar, S.
|Issue Date:||8-Oct-2013||Citation:||Maity, A., Yadav, S., Verma, C.S., Ghosh Dastidar, S. (2013-10-08). Dynamics of Bcl-xL in Water and Membrane: Molecular Simulations. PLoS ONE 8 (10) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0076837||Abstract:||The Bcl2 family of proteins is capable of switching the apoptotic machinery by directly controlling the release of apoptotic factors from the mitochondrial outer membrane. They have 'pro' and 'anti'-apoptotic subgroups of proteins which antagonize each other's function; however a detailed atomistic understanding of their mechanisms based on the dynamical events, particularly in the membrane, is lacking. Using molecular dynamics simulations totaling 1.6μs we outline the major differences between the conformational dynamics in water and in membrane. Using implicit models of solvent and membrane, the simulated results reveal a picture that is in agreement with the 'hit-and run' concept which states that BH3-only peptides displace the tail (which acts as a pseudo substrate of the protein itself) from its binding pocket; this helps the membrane association of the protein after which the BH3 peptide becomes free. From simulations, Bcl-xL appears to be auto-inhibited by its C-terminal tail that embeds into and covers the hydrophobic binding pocket. However the tail is unable to energetically compete with BH3-peptides in water. In contrast, in the membrane, neither the tail nor the BH3-peptides are stable in the binding pocket and appear to be easily dissociated off as the pocket expands in response to the hydrophobic environment. This renders the binding pocket large and open, thus receptive to interactions with other protein partners. Principal components of the motions are dramatically different in the aqueous and in the membrane environments and provide clues regarding the conformational transitions that Bcl-xL undergoes in the membrane, in agreement with the biochemical data. © 2013 Maity et al.||Source Title:||PLoS ONE||URI:||http://scholarbank.nus.edu.sg/handle/10635/100515||ISSN:||19326203||DOI:||10.1371/journal.pone.0076837|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Feb 18, 2020
WEB OF SCIENCETM
checked on Feb 18, 2020
checked on Feb 16, 2020
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.