Cloning and chromosomal localization of mouse keratocan, a corneal keratan sulfate proteoglycan
Cloning and chromosomal localization of mouse keratocan, a corneal keratan sulfate proteoglycan
复制标题
DOI：
10.1007/s003359900757
复制
发表时间：
1998-04-01
期刊：
影响因子：
2.5
通讯作者：
Hassell, JR
中科院分区：
文献类型：
--
作者：
Dunlevy, JR;Chakravarti, S;Hassell, JR
角膜基质由一种高度结构化的细胞外基质组成，这种基质由称为角质细胞的特殊成纤维细胞维持。角膜的透明度依赖于高度硫酸化的蛋白多糖(PG)的存在，它可以结合胶原并调节胶原纤维的直径(Rada等人)。1993年)。已被鉴定的角膜蛋白多糖含有大量富含亮氨酸的重复序列，它们都属于同一个基因家族，即Leurich蛋白多糖(LRP)。其中包括一种软骨素/硫酸皮肤素蛋白多糖(CS/DSPG)、核心蛋白聚糖和三种硫酸角蛋白多糖(KSPG)、鲁米肯、角质聚糖和骨粘素(Funderburgh等人)。1991年，1993年；Blochberger等人。1992年；Corpuz等人。1996年)。角膜KSPG是角膜透明前早期角膜发育过程中的糖蛋白(Cornuet et al.和I型黄斑性角膜营养不良，这是一种以角膜混浊和沉积为特征的遗传性疾病(Klintworth等人)。1977,1983；Nakazawa等人。1984年)。这些先前的研究表明，角膜透明度与角蛋白硫酸盐的存在直接相关。核心蛋白和聚乳糖胺侧链本身似乎不足以维持角膜的透明结构。角化蛋白的一级结构，基于从牛和鸡的cDNA序列推导的氨基酸序列，显示N-末端和C-末端的球状结构域，包含四个和两个半胱氨酸残基，分别形成两个和一个二硫键，以及11个高度保守的富含亮氨酸的重复序列，主要位于这两个球状结构域之间(Corpuz等人)。1996年；Dunlevy等人。1998年)。鸡角化蛋白的二维模型，基于核糖核酸酶抑制物的X射线晶体结构，核糖核酸酶抑制物是一种完全由富含亮氨酸的重复序列组成的分子，(Kobe等人。1993,1995)，显示了富含Leu的重复序列与这些区域螺旋状盘绕在一起，形成了马蹄形结构(Dunlevy等人)。1998年)。这个模型还显示，三条KS链中有两条从马蹄铁的外表面向外延伸，内表面更有可能参与胶原结合。
The corneal stroma consists of a highly structured extracellular matrix that is maintained by specialized fibroblasts called keratocytes. The transparency of the cornea is dependent on the presence of highly sulfated proteoglycans (PG) that can bind collagen and can regulate collagen fibril diameter (Rada et al. 1993). The corneal proteoglycans that have been identified contain numerous Leu-rich repeats and all belong to the same gene family, the Leurich proteoglycans (LRP). These include a chondroitin/dermatan sulfate proteoglycan (CS/DSPG), decorin, and three keratan sulfate proteoglycans (KSPG), lumican, keratocan, and osteoglycin (Funderburgh et al. 1991, 1993; Blochberger et al. 1992; Corpuz et al. 1996). The corneal KSPGs are glycoproteins exclusively during early corneal development before corneal transparency (Cornuet et al. 1994) and in macular corneal dystrophy type I, an inherited disease that is characterized by corneal opacity and deposits (Klintworth et al. 1977, 1983; Nakazawa et al. 1984). These previous studies show a direct correlation between corneal transparency and the presence of keratan sulfate. The core protein and poly-lactosamine side chains alone appear to be insufficient extracellular matrix components for sustaining a transparent structure in the cornea.The primary structure of keratocan, based on the deduced amino acid sequence from bovine and chick cDNA sequences, shows N-and C-terminal globular domains containing four and two Cys residues forming two and one disulfide bond, respectively, and 11 highly conserved Leu-rich repeats located mainly between the two globular domains (Corpuz et al. 1996; Dunlevy et al. 1998). The two-dimensional model of chick keratocan, based on the X-ray crystallography structure of ribonuclease inhibitor, a molecule comprised entirely of Leu-rich repeats,(Kobe et al. 1993, 1995), shows the Leu-rich repeats coiled in a spiral with these regions in close proximity to each other, forming a horseshoe structure (Dunlevy et al. 1998). This model also shows two out of three KS chains extended outward from the outer surface of the horseshoe with the inner surface more likely to be involved in collagen binding.