R Sankararamakrishnan
Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, U. P., India.


Apoptosis is an important physiological process in which unnecessary and malfunctioning of the cells are removed in a controlled and regulated fashion in multicellular organisms. The Bcl-2 family of proteins regulates the intrinsic apoptotic pathway. The balance in the expression of pro- and anti-apoptotic Bcl-2 proteins plays a central role in the mitochondrial outer membrane permeabilization. Bcl-2 proteins have four sequence homology regions BH1 to BH4. The BH3 region of pro-apoptotic Bcl2 proteins binds to the hydrophobic groove of anti-apoptotic Bcl-2 proteins. An anti-apoptotic Bcl-2 protein can have several pro-apoptotic Bcl-2 partners with different binding affinities. The mechanism of protein-protein recognition among the Bcl-2 proteins is a major research area that helps in the design of anti-cancer drugs specific to a particular Bcl-2 target. In this talk, I will describe multiple molecular dynamics simulations of Bcl-XL, an anti-apoptotic Bcl-2 protein. The apo-form and the complex structures, in which the bound peptides were removed, were considered for the simulations. Our simulations show that the hydrophobic groove of Bcl-XL is flexible. In the absence of a ligand, the loop connecting the helices H2 and H3 tries to shield the hydrophobic groove from the solvent. Results of these studies highlight the differences in the behaviour of Bcl-XL in free and complex forms. The plasticity exhibited by the hydrophobic groove of Bcl-XL is crucial for the protein to bind several pro-apoptotic Bcl-2 proteins. Read More …

Please follow and like us:
News Reporter