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

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.