Bost F, Diarra-Mehrpour M, Martin J P
INSERM U.295, Faculté de Médecine Pharmacie de Rouen, St Etienne du Rouvray, France.
Eur J Biochem. 1998 Mar 15;252(3):339-46. doi: 10.1046/j.1432-1327.1998.2520339.x.
Extracellular matrix (ECM) is composed of several macromolecules associated in a complex network. This structure allows cells to adhere, migrate and interact. Hyaluronic acid (HA) is a glycosaminoglycan (GAG) and a major representative of ECM. HA-binding proteins such as CD44, aggrecan, and versican, have been implicated in structuring the ECM by stabilizing large macromolecular aggregates. They also play an important role in tumor metastasis and cell motility. Recently, further HA-binding proteins were identified: the inter-alpha-trypsin inhibitor(ITI)-related proteins. ITI is a glycoprotein composed of three polypeptides: two heavy chains (HC1 and HC2) and one light chain (bikunin). Bikunin confers the protease-inhibitor function. The heavy chains' function was unknown. Recent studies have shown that HC1 and HC2 are linked in vivo and in vitro to hyaluronic acid. This linkage greatly improves extracellular matrix stability. It also demonstrates that ITI-related proteins might be considered as HA-binding proteins (HABP). The ITI related proteins are composed of four polypeptides (HC1, HC2, HC3 and the bikunin) encoded by four genes H1, H2, H3 and L. Unlike the majority of plasma protein a non-disulfide covalent linkage exists between heavy chains and bikunin. This review presents the recent progress concerning the interactions between ITI and ECM showing that ITI-related proteins are HABP members. We will focus on the heavy chain linkage with HA, which represents the demonstration of covalent binding between proteins and HA.
细胞外基质（ECM）由复杂网络中相互关联的几种大分子组成。这种结构使细胞能够黏附、迁移和相互作用。透明质酸（HA）是一种糖胺聚糖（GAG），也是ECM的主要代表。诸如CD44、聚集蛋白聚糖和多功能蛋白聚糖等HA结合蛋白，通过稳定大分子聚集体参与ECM的构建。它们在肿瘤转移和细胞运动中也起着重要作用。最近，又鉴定出了更多的HA结合蛋白：α-胰蛋白酶抑制剂（ITI）相关蛋白。ITI是一种糖蛋白，由三条多肽组成：两条重链（HC1和HC2）和一条轻链（比基尼）。比基尼具有蛋白酶抑制功能。重链的功能尚不清楚。最近的研究表明，HC1和HC2在体内和体外都与透明质酸相连。这种连接大大提高了细胞外基质的稳定性。这也表明ITI相关蛋白可能被视为HA结合蛋白（HABP）。ITI相关蛋白由四个基因H1、H2、H3和L编码的四条多肽（HC1、HC2、HC3和比基尼）组成。与大多数血浆蛋白不同，重链和比基尼之间存在非二硫键共价连接。本综述介绍了有关ITI与ECM相互作用的最新进展，表明ITI相关蛋白是HABP成员。我们将重点关注重链与HA的连接，这代表了蛋白质与HA之间共价结合的证明。
