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    Deconstructing the DGAT1 enzyme: membrane interactions at substrate binding sites

    Deschenes, R.J. and Lopes, J.L.S. and Beltramini, L.M. and Wallace, Bonnie A. and Araujo, A.P.U. (2015) Deconstructing the DGAT1 enzyme: membrane interactions at substrate binding sites. PLOS ONE 10 (2), e0118407. ISSN 1932-6203.

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    Abstract

    Diacylglycerol acyltransferase 1 (DGAT1) is a key enzyme in the triacylglyceride synthesis pathway. Bovine DGAT1 is an endoplasmic reticulum membrane-bound protein associated with the regulation of fat content in milk and meat. The aim of this study was to evaluate the interaction of DGAT1 peptides corresponding to putative substrate binding sites with different types of model membranes. Whilst these peptides are predicted to be located in an extramembranous loop of the membrane-bound protein, their hydrophobic substrates are membrane-bound molecules. In this study, peptides corresponding to the binding sites of the two substrates involved in the reaction were examined in the presence of model membranes in order to probe potential interactions between them that might influence the subsequent binding of the substrates. Whilst the conformation of one of the peptides changed upon binding several types of micelles regardless of their surface charge, suggesting binding to hydrophobic domains, the other peptide bound strongly to negatively-charged model membranes. This binding was accompanied by a change in conformation, and produced leakage of the liposome-entrapped dye calcein. The different hydrophobic and electrostatic interactions observed suggest the peptides may be involved in the interactions of the enzyme with membrane surfaces, facilitating access of the catalytic histidine to the triacylglycerol substrates.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Bioinformatics, Bloomsbury Centre for, Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 02 Mar 2015 08:08
    Last Modified: 07 Dec 2016 15:05
    URI: http://eprints.bbk.ac.uk/id/eprint/11764

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