Bijl E, van Valenberg H J F, Huppertz T, van Hooijdonk A C M, Bovenhuis H
Dairy Science and Technology Group, Wageningen University, PO Box 17, 6700 AA, Wageningen, the Netherlands.
NIZO Food Research, PO Box 20, 6710 BA, Ede, the Netherlands.
J Dairy Sci. 2014 Nov;97(11):7240-6. doi: 10.3168/jds.2014-8061. Epub 2014 Sep 6.
Casein phosphorylation is a posttranslational modification catalyzed by kinase enzymes that attach phosphate groups to specific AA in the protein sequence. This modification is one of the key factors responsible for the stabilization of calcium phosphate nanoclusters in casein micelles and for the internal structure of the casein micelles. α(S1)-Casein (α(s1)-CN) is of special interest because it constitutes up to 40% of the total casein fraction in milk, and it has 2 common phosphorylation states, with 8 (α(S1)-CN-8P) and 9 (α(S1)-CN-9P) phosphorylated serine residues. Factors affecting this variation in the degree of phosphorylation are not currently known. The objective of this research was to determine the genetic background of α(S1)-CN-8P and α(S1)-CN-9P. The genetic and phenotypic correlation between α(S1)-CN-8P and α(S1)-CN-9P was low (0.18 and 0.19, respectively). This low genetic correlation suggests a different genetic background. These differences were further investigated by means of a genome-wide association study, which showed that both α(S1)-CN-8P and α(S1)-CN-9P were affected by a region on Bos taurus autosome (BTA) 6, but only α(S1)-CN-8P was affected by a region on BTA11 that contains the gene that encodes for β-lactoglobulin (β-LG), and only α(S1)-CN-9P was affected by a region on BTA14 that contains the diacylglycerol acyltransferase 1 (DGAT1) gene. Estimated effects of β-LG protein genotypes showed that only α(S1)-CN-8P was associated with the β-LG A/B polymorphism (g.1772G>A and g.3054C>T); the AA genotype of β-LG was associated with a lower concentration of α(S1)-CN-8P (-0.32% wt/wt) than the BB genotype (+0.41% wt/wt). Estimated effects of DGAT1 K232A genotypes showed that only α(S1)-CN-9P was associated with the DGAT1 gene polymorphism; DGAT1 AA genotype was associated with a higher α(S1)-CN-9P concentration (+0.53% wt/wt) than the DGAT1 KK genotype (-0.44% wt/wt). The results give insight in phosphorylation of α(S1)-CN-8P and α(S1)-CN-9P, which seem to be regulated by a different set of genes.
酪蛋白磷酸化是一种翻译后修饰，由激酶催化，将磷酸基团连接到蛋白质序列中的特定氨基酸上。这种修饰是酪蛋白胶束中磷酸钙纳米簇稳定以及酪蛋白胶束内部结构形成的关键因素之一。α(S1)-酪蛋白（α(s1)-CN）特别受关注，因为它占牛奶中酪蛋白总量的40%，并且有两种常见的磷酸化状态，分别具有8个（α(S1)-CN-8P）和9个（α(S1)-CN-9P）磷酸化丝氨酸残基。目前尚不清楚影响这种磷酸化程度变化的因素。本研究的目的是确定α(S1)-CN-8P和α(S1)-CN-9P的遗传背景。α(S1)-CN-8P和α(S1)-CN-9P之间的遗传和表型相关性较低（分别为0.18和0.19）。这种低遗传相关性表明存在不同的遗传背景。通过全基因组关联研究进一步研究了这些差异，结果表明α(S1)-CN-8P和α(S1)-CN-9P均受牛6号常染色体（BTA）上一个区域的影响，但只有α(S1)-CN-8P受BTA11上一个包含编码β-乳球蛋白（β-LG）基因的区域影响，只有α(S1)-CN-9P受BTA14上一个包含二酰基甘油酰基转移酶1（DGAT1）基因的区域影响。β-LG蛋白基因型的估计效应表明，只有α(S1)-CN-8P与β-LG A/B多态性（g.1772G>A和g.3054C>T）相关；β-LG的AA基因型与α(S1)-CN-8P的较低浓度（-0.32% wt/wt）相关，而BB基因型则与较高浓度（+0.41% wt/wt）相关。DGAT1 K232A基因型的估计效应表明，只有α(S1)-CN-9P与DGAT1基因多态性相关；DGAT1的AA基因型与α(S1)-CN-9P的较高浓度（+0.53% wt/wt）相关，而KK基因型则与较低浓度（-0.44% wt/wt）相关。这些结果为α(S1)-CN-8P和α(S1)-CN-9P的磷酸化提供了见解，它们似乎受不同基因集的调控。
