High-molecular-weight precursor of epidermal filaggrin and hypothesis for its tandem repeating structure.
High-molecular-weight precursor of epidermal filaggrin and hypothesis for its tandem repeating structure.
复制标题
表皮丝聚蛋白的高分子量前体及其串联重复结构的假设。
DOI：
10.1021/bi00301a034
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发表时间：
1984
期刊：
影响因子：
2.9
通讯作者：
Dale,BA
中科院分区：
文献类型：
--
作者：
Lonsdale-Eccles,JD;Resing,KA;Meek,RL;Dale,BA
摘要：微丝蛋白是一种富含组氨酸的蛋白质，与哺乳动物表皮角质化密切相关。使用免疫学和体内脉冲追逐研究相结合的放射性标记组氨酸和磷酸盐，我们发现大鼠和小鼠微丝蛋白的磷酸化前体的表观分子量比以前认识到的要高得多(分别为6×105和3.9×105)。这些高相对分子质量的微丝蛋白前体可以被组氨酸快速标记，并在去图灵条件下从表皮中提取。在注射后24小时，尽管丝状颗粒的尺寸小于前体的10%，但在注射后24小时，在前体中结合的标记的一半以上仍存在于微丝颗粒中。在体外对前体进行有限的蛋白质降解会形成一系列寡聚肽，其基础是一段略大于微丝蛋白本身的磷酸化片段。Filaggrin是一种从皮肤角质层分离出来的蛋白质(Dale，1977；Ball等人，1978；Steinert等人，1981)。它与表皮角蛋白细丝聚集，显然在角化细胞中起角蛋白基质的作用(Dale等人，1978；Steinert等人，1981；Lynley和Dale，1983)。脉冲追逐研究表明，微丝蛋白来源于角化透明质酸颗粒(Dale&Ling，1979)提取物中的一种前体，即布通状微丝蛋白，其前体含量很高。
John D. Lonsdale-Eccles,* Katheryn A. Resing, Rick L. Meek, and Beverly A. Dale* abstract: Filaggrin is a histidine-rich protein that is inti-mately involved in mammalian epidermal keratinization. Using a combination of immunologic and in vivo pulse-chase studies with radiolabeled histidine and phosphate, we show that the phosphorylated precursor of both rat and mouse filaggrin has an apparent molecular weight much higher than previously realized (6 X 105 and 3.9 X 105, respectively). These highmolecular-weight filaggrin precursors can be rapidly labeled with histidine and extracted from the epidermis under dena-turing conditions. More than half of the label incorporated in the precursor at 2 h is found in filaggrin at 24 h after injection, even though filaggrin is less than 10% of the size of the precursor. Limited proteolytic digestion of the precursor in vitro results in the formation of an oligomeric series of peptides based on a phosphorylated fragment slightly larger than filaggrin itself. More extensive digestion of this fragmentFilaggrin is a protein isolated from the stratum corneum of skin (Dale, 1977; Ball et al., 1978; Steinert et al., 1981). It aggregates with epidermal keratin filaments and apparently functions as the keratin matrix in the cornified cells (Dale et al., 1978; Steinert et al., 1981; Lynley& Dale, 1983). Pulse-chase studies have shown that filaggrin is derived from a precursor located in extracts of keratohyalin granules (Dale & Ling, 1979), butunlike filaggrin, the precursor is highly