Functional characterization of a SNP (F51S) found in human alpha 1-antitrypsin.
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ABSTRACT: Background
Alpha 1-antitrypsin (A1AT) deficiency is related to lung and liver diseases, including pulmonary emphysema and liver cirrhosis in humans. Genetic variations including single nucleotide polymorphisms (SNPs) of SERPINA1 are responsible for A1AT deficiency, but the characteristics of the SNPs are not well-understood. Here, we investigated the features of a rare SNP (F51S) of A1AT, which introduces an additional N-glycosylation site in the N-terminal region of A1AT.Methods
We evaluated the F51S variant compared with the wild-type (WT) A1AT with regard to expression in CHO-K1 cells, trypsin inhibitory activity, polymerization, and thermal stability.Results
The recombinant F51S protein expressed in CHO-K1 cells was mostly retained inside cells. The F51S variant had trypsin inhibitory activity, but reduced thermal stability compared with the WT A1AT. The native acrylamide gel data showed that F51S tended to prevent polymerization of A1AT.Conclusion
The results of this study indicate that Phe51 and the surrounding hydrophobic residue cluster plays an important role in the conformation and secretion of A1AT and suggest the harmful effects of a rare F51S SNP in human health.
SUBMITTER: Trinh HN
PROVIDER: S-EPMC6687665 | biostudies-literature | 2019 Aug
REPOSITORIES: biostudies-literature
Publications
Functional characterization of a SNP (F51S) found in human alpha 1-antitrypsin.
Trinh Hong-Nhung HN Jang Sei-Heon SH Lee ChangWoo C
Molecular genetics & genomic medicine 20190628 8
<h4>Background</h4>Alpha 1-antitrypsin (A1AT) deficiency is related to lung and liver diseases, including pulmonary emphysema and liver cirrhosis in humans. Genetic variations including single nucleotide polymorphisms (SNPs) of SERPINA1 are responsible for A1AT deficiency, but the characteristics of the SNPs are not well-understood. Here, we investigated the features of a rare SNP (F51S) of A1AT, which introduces an additional N-glycosylation site in the N-terminal region of A1AT.<h4>Methods</h4 ...[more]
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