In silico engineering of aggregation-prone recombinant proteins for substrate recognition by the chaperonin GroEL

BMC Genomics

Proceedings

Durai Sundar¹  Ankita Punetha²  Tapan K Chaudhuri³  Vipul Kumar³ 

[1] Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, 110016, Hauz Khas, New Delhi, India;Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, 110016, Hauz Khas, New Delhi, India;Department of Biotechnology, Indian Institute of Technology Guwahati, 781039, Guwahati, India;School of Biological Sciences, Indian Institute of Technology Delhi, 110016, Hauz Khas, New Delhi, India;

关键词: Hydrophobic Patch;    Charged Amino Acid Residue;    Aggregation Propensity;    Chaperonin GroEL;    Hydropathy Index;   

DOI  :  10.1186/1471-2164-13-S7-S22

来源: Springer

【 摘 要 】

BackgroundMolecular chaperones appear to have been evolved to facilitate protein folding in the cell through entrapment of folding intermediates on the interior of a large cavity formed between GroEL and its co-chaperonin GroES. They bind newly synthesized or non-native polypeptides through hydrophobic interactions and prevent their aggregation. Some proteins do not interact with GroEL, hence even though they are aggregation prone, cannot be assisted by GroEL for their folding.ResultsIn this study, we have attempted to engineer these non-substrate proteins to convert them as the substrate for GroEL, without compromising on their function. We have used a computational biology approach to generate mutants of the selected proteins by selectively mutating residues in the hydrophobic patch, similar to GroES mobile loop region that are responsible for interaction with GroEL, and compared with the wild counterparts for calculation of their instability and aggregation propensities. The energies of the newly designed mutants were computed through molecular dynamics simulations. We observed increased aggregation propensity of some of the mutants formed after replacing charged amino acid residues with hydrophobic ones in the well defined hydrophobic patch, raising the possibility of their binding ability to GroEL.ConclusionsThe newly generated mutants may provide potential substrates for Chaperonin GroEL, which can be experimentally generated and tested for their tendency of aggregation, interactions with GroEL and the possibility of chaperone-assisted folding to produce functional proteins.

【 授权许可】

Unknown   
© Kumar et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.