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揭示奶牛 DGAT1 错义 nsSNP 的结构和构象动态。

Unraveling structural and conformational dynamics of DGAT1 missense nsSNPs in dairy cattle.

机构信息

Department of Animal Science and Technology, Chung-Ang University, Anseong-si, Gyeonggi-do, 17546, Republic of Korea.

出版信息

Sci Rep. 2022 Mar 22;12(1):4873. doi: 10.1038/s41598-022-08833-6.

DOI:10.1038/s41598-022-08833-6
PMID:35318385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8940929/
Abstract

Cattle are domestic animals that have been nourishing humans for thousands of years. Milk from cattle represents a key source of high-quality protein, fat, and other nutrients. The nutritional value of milk and dairy products is closely associated with the fat content, providing up to 30% of the total fat consumed in the human diet. The fat content in cattle milk represents a major concern for the scientific community due to its association with human health. The relationship between milk fat content and diacylglycerol o-acyltransferase 1 gene (DGAT1) is well described in literature. Several studies demonstrated the difference in fat contents and other milk production traits in a wide range of cattle breeds, to be associated with missense non-synonymous single nucleotide polymorphisms (nsSNPs) of the DGAT1 gene. As a result, an nsSNPs analysis is crucial for unraveling the DGAT1 structural and conformational dynamics linked to milk fat content. DGAT1-nsSNPs are yet to be studied in terms of their structural and functional impact. Therefore, state-of-the-art computational and structural genomic methods were used to analyze five selected variants (W128R, W214R, C215G, P245R, and W459G), along with the wild type DGAT1. Significant structural and conformational changes in the variants were observed. We illustrate how single amino acid substitutions affect DGAT1 function, how this contributes to our understanding of the molecular basis of variations in DGAT1, and ultimately its impact in improving fat quality in milk.

摘要

牛是已经为人类提供了数千年营养的家畜。牛奶是高质量蛋白质、脂肪和其他营养物质的主要来源。牛奶和奶制品的营养价值与脂肪含量密切相关,提供了人类饮食中总脂肪摄入量的 30%。由于与人类健康有关,牛奶脂肪含量一直是科学界关注的主要问题。文献中详细描述了牛奶脂肪含量与二酰基甘油酰基转移酶 1 基因(DGAT1)之间的关系。多项研究表明,在广泛的牛品种中,脂肪含量和其他牛奶生产性状的差异与 DGAT1 基因的错义非同义单核苷酸多态性(nsSNPs)有关。因此,nsSNPs 分析对于揭示与牛奶脂肪含量相关的 DGAT1 结构和构象动力学至关重要。DGAT1-nsSNPs 的结构和功能影响仍有待研究。因此,使用最先进的计算和结构基因组学方法来分析了五个选定的变体(W128R、W214R、C215G、P245R 和 W459G),以及野生型 DGAT1。观察到变体的显著结构和构象变化。我们说明了单氨基酸取代如何影响 DGAT1 功能,以及这如何帮助我们理解 DGAT1 变异的分子基础,并最终影响提高牛奶中的脂肪质量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/b47e711d765f/41598_2022_8833_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/f66f54df3aa1/41598_2022_8833_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/b50be6d5845a/41598_2022_8833_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/c8b253b5b22d/41598_2022_8833_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/485d4b2f6422/41598_2022_8833_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/443655485da3/41598_2022_8833_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/3c1acffbe615/41598_2022_8833_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/19d9bd07adac/41598_2022_8833_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/b47e711d765f/41598_2022_8833_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/f66f54df3aa1/41598_2022_8833_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/b50be6d5845a/41598_2022_8833_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/c8b253b5b22d/41598_2022_8833_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/485d4b2f6422/41598_2022_8833_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/443655485da3/41598_2022_8833_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/3c1acffbe615/41598_2022_8833_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/19d9bd07adac/41598_2022_8833_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cef1/8940929/b47e711d765f/41598_2022_8833_Fig8_HTML.jpg

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