Sasaki M, Kleinman H K, Huber H, Deutzmann R, Yamada Y
Laboratory of Developmental Biology and Anomalies, National Institute of Dental Research, Bethesda, Maryland 20892.
J Biol Chem. 1988 Nov 15;263(32):16536-44.
Laminin (Mr = 800,000) is a glycoprotein consisting of three chains, A, B1, and B2, and has diverse biological activities. Previously we reported the complete primary structure of the B1 and B2 chains of mouse laminin deduced from cDNA sequence (Sasaki, M., Kohno, K., Kato, S., Martin, G. R., and Yamada, Y. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 935-939; Sasaki, M., and Yamada, Y. (1988) J. Biol. Chem. 262, 17111-17117). Here we describe the isolation, characterization, and sequence of cDNA clones spanning 9,520 bases which encode the entire A chain of mouse laminin. The nucleotide sequence of the clones contains an open reading frame of 3,084 amino acids including 24 amino acids of a signal peptide. The A chain contains some eight distinct domains including alpha-helices, cysteine-rich repeats and globules. There is considerable sequence and structural homology between the A chain and the B1 and B2 chains. However, the A chain has a unique globular structure containing homologous repeats at the carboxyl terminus and constituting one third of the molecular mass of the chain. Furthermore, the A chain contains three globules and three cysteine-rich domains at the amino terminus, whereas the B1 and B2 chains have only two each of such domains. The A chain shows homology to the basement membrane heparan sulfate proteoglycan core protein and the extracellular domain of the Drosophila neurogenic protein Notch. There is an RGD (Arg-Gly-Asp) sequence in one of the cysteine-rich domains of the A chain. This potential cell binding sequence could be active as another adhesion signal in addition to the previously identified cell binding sequence YIGSR (Tyr-Ile-Gly-Ser-Arg) of the B1 chain.
层粘连蛋白（分子量 = 800,000）是一种由A、B1和B2三条链组成的糖蛋白，具有多种生物学活性。此前我们报道了从小鼠层粘连蛋白cDNA序列推导得出的B1和B2链的完整一级结构（佐佐木，M.， Kohno，K.，加藤，S.，马丁，G. R.，以及山田，Y.（1987年）《美国国家科学院院刊》84，935 - 939；佐佐木，M.，以及山田，Y.（1988年）《生物化学杂志》262，17111 - 17117）。在此我们描述了跨越9520个碱基的cDNA克隆的分离、特性鉴定及序列分析，这些克隆编码小鼠层粘连蛋白的整条A链。克隆的核苷酸序列包含一个3084个氨基酸的开放阅读框，其中包括24个氨基酸的信号肽。A链包含大约八个不同的结构域，包括α - 螺旋、富含半胱氨酸的重复序列和球状结构。A链与B1和B2链之间存在相当程度的序列和结构同源性。然而，A链具有独特的球状结构，在羧基末端含有同源重复序列，占该链分子量的三分之一。此外，A链在氨基末端含有三个球状结构和三个富含半胱氨酸的结构域，而B1和B2链各自仅含有两个这样的结构域。A链与基底膜硫酸乙酰肝素蛋白聚糖核心蛋白以及果蝇神经源性蛋白Notch的细胞外结构域具有同源性。A链的一个富含半胱氨酸的结构域中存在一个RGD（精氨酸 - 甘氨酸 - 天冬氨酸）序列。除了先前鉴定出的B1链的细胞结合序列YIGSR（酪氨酸 - 异亮氨酸 - 甘氨酸 - 丝氨酸 - 精氨酸）外，这个潜在的细胞结合序列可能作为另一种黏附信号发挥作用。
