Functional characterization of a SNP (F51S) found in human alpha 1‐antitrypsin
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 o...
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| Format: | Article |
| Language: | English |
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Wiley
2019-08-01
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| Series: | Molecular Genetics & Genomic Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mgg3.819 |
| _version_ | 1798016769406795776 |
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| author | Hong‐Nhung Trinh Sei‐Heon Jang ChangWoo Lee |
| author_facet | Hong‐Nhung Trinh Sei‐Heon Jang ChangWoo Lee |
| author_sort | Hong‐Nhung Trinh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T15:54:59Z |
| format | Article |
| id | doaj.art-abd3c027fb9b4a64bd6645cc35a758f6 |
| institution | Directory Open Access Journal |
| issn | 2324-9269 |
| language | English |
| last_indexed | 2024-04-11T15:54:59Z |
| publishDate | 2019-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Genetics & Genomic Medicine |
| spelling | doaj.art-abd3c027fb9b4a64bd6645cc35a758f62022-12-22T04:15:11ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-08-0178n/an/a10.1002/mgg3.819Functional characterization of a SNP (F51S) found in human alpha 1‐antitrypsinHong‐Nhung Trinh0Sei‐Heon Jang1ChangWoo Lee2Department of Biomedical Science and Center for Bio‐Nanomaterials Daegu University Gyeongsan South KoreaDepartment of Biomedical Science and Center for Bio‐Nanomaterials Daegu University Gyeongsan South KoreaDepartment of Biomedical Science and Center for Bio‐Nanomaterials Daegu University Gyeongsan South KoreaAbstract 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.https://doi.org/10.1002/mgg3.819Alpha 1‐antitrypsin deficiencyF51Spolymerizationsingle nucleotide polymorphismthermal stability |
| spellingShingle | Hong‐Nhung Trinh Sei‐Heon Jang ChangWoo Lee Functional characterization of a SNP (F51S) found in human alpha 1‐antitrypsin Molecular Genetics & Genomic Medicine Alpha 1‐antitrypsin deficiency F51S polymerization single nucleotide polymorphism thermal stability |
| title | Functional characterization of a SNP (F51S) found in human alpha 1‐antitrypsin |
| title_full | Functional characterization of a SNP (F51S) found in human alpha 1‐antitrypsin |
| title_fullStr | Functional characterization of a SNP (F51S) found in human alpha 1‐antitrypsin |
| title_full_unstemmed | Functional characterization of a SNP (F51S) found in human alpha 1‐antitrypsin |
| title_short | Functional characterization of a SNP (F51S) found in human alpha 1‐antitrypsin |
| title_sort | functional characterization of a snp f51s found in human alpha 1 antitrypsin |
| topic | Alpha 1‐antitrypsin deficiency F51S polymerization single nucleotide polymorphism thermal stability |
| url | https://doi.org/10.1002/mgg3.819 |
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