Structure, function and phylogeny of zinc-α2-glycoprotein in health and disease
AuthorsAllen, Samantha Jayne
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AbstractZinc-α2-glycoprotein (ZAG) is a 42kDa non-classical major histocompatibility complex (MHC) class I adipokine excreted around the body that regulates body mass through lipid metabolism. Abnormal expression of ZAG occurs in diseases such as cachexia and obesity, with studies suggesting that ZAG has a potential use as a biomarker in the identification of cancer. Recent literature has identified binding sites within the groove of the α1α2 domain and, unexpectedly, in the α3 domain when bound in a tetramer. To identify these sites and investigate the α3 domain’s ability to form a β-barrel, recombinant ZAG was expressed from a pET-23a(+) plasmid in a BL21 DE3 Star pRARE E.coli host. Whilst this investigation was interrupted due to COVID-19, other characteristics of ZAG were investigated. Phylogenetic analysis revealed that ZAG was more closely related to non-classical MHC class I related proteins MICA, MICB, HLA-A, -E, -F, -G and MR1, and evolved linearly with placental mammals, where marsupial mammalian ZAG is more diverged. An interactive ZAG database allowing for the observational analysis of variant mutations in ZAG from cancer patients was developed, revealing that mutations in the RGD triad and lipid binding residues may cause metabolic changes that are required for the progression of cancer.
CitationAllen, S. (2021) 'Structure, Function and Phylogeny of Zinc-α2-Glycoprotein in Health and Disease'. MSc By Research thesis. University of Bedfordshire.
PublisherUniversity of Bedfordshire
TypeThesis or dissertation
DescriptionA thesis submitted to the University of Bedfordshire in fulfilment of the requirements for the degree of Masters by Research.
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