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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Conversion of alpha-lactalbumin to a protein inducing apoptosis
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Conversion of alpha-lactalbumin to a protein inducing apoptosis

机译：α-乳清蛋白转化为诱导细胞凋亡的蛋白质

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In this study alpha-lactalbumin was converted from the regular, native state to a folding variant with altered biological function. The folding variant was shown to induce apoptosis in tumor cells and immature cells. but healthy cells were resistant to this effect. Conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells) required partial unfolding of the protein and a specific fatty acid, C18:1, as a necessary cofactor. Conversion was achieved with alpha-lactalbumin derived from human milk whey and with recombinant protein expressed in Escherichia coli. We thus have identified the folding change and the fatty acid as two key elements that define HAMLET, the apoptosis-inducing functional state of alpha-lactalbumin. Although the environment in the mammary gland favors the native conformation of alpha-lactalbumin that serves as a specifier in the lactose synthase complex. the conditions under which HAMLET was formed resemble those in the stomach of the nursing child. Low pH is known to release Ca2+ from the high- affinity Ca2+-binding site and to activate lipases that hydrolyze free fatty acids from milk triglycerides. We propose that this single amino acid polypeptide chain may perform vastly different bio- logical functions depending on its folding state and the in vivo environment. It may be speculated that molecules like HAMLET can aid in lowering the incidence of cancer in breast-fed children by purging of tumor cells from the gut of the neonate.
机译：在这项研究中，α-乳白蛋白从正常的天然状态转变为具有改变的生物学功能的折叠变体。该折叠变体显示出在肿瘤细胞和未成熟细胞中诱导凋亡。但是健康的细胞对此具有抵抗力。转化为HAMLET（对肿瘤细胞具有致死性的人α-乳清蛋白）需要蛋白质和特定脂肪酸C18：1的部分展开，作为必需的辅因子。用衍生自人乳清的α-乳清蛋白和在大肠杆菌中表达的重组蛋白实现了转化。因此，我们已经确定折叠变化和脂肪酸是定义HAMLET的两个关键元素，HAMLET是诱导α-乳白蛋白凋亡的功能状态。尽管乳腺中的环境有利于α-乳白蛋白的天然构象，该构象在乳糖合酶复合物中起指示作用。形成哈姆雷特的条件类似于哺乳期儿童的胃部条件。已知低pH值会从高亲和力的Ca2 +结合位点释放Ca2 +，并激活脂肪酶，从而水解甘油三酸酯中的游离脂肪酸。我们提出，根据其折叠状态和体内环境，该单氨基酸多肽链可能执行截然不同的生物学功能。可以推测，诸如HAMLET之类的分子可以通过清除新生儿肠道中的肿瘤细胞来帮助降低母乳喂养儿童的癌症发病率。

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