Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40
Crystal structure of a pair of follistatin-like and EF-hand calcium-binding domains in BM-40
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DOI：
10.1093/emboj/16.13.3778
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发表时间：
1997-07-01
期刊：
影响因子：
11.4
通讯作者：
Timpl, R
中科院分区：
文献类型：
--
作者：
Hohenester, E;Maurer, P;Timpl, R
BM-40(也称为SPARC或Osteonectin)是一种参与组织重塑的抗粘连分泌糖蛋白。BM-40除了一个酸性的N-末端片段外，还包括一个卵泡抑素样(FS)结构域和一个EF-手钙结合(EC)结构域。在这里，我们报道了人BM-40的FS-EC结构域对在3.1埃分辨率下的晶体结构，这两个不同的结构域通过一个涉及EC结构域的EF-Hand对的小界面相互作用。与细胞结合、抑制细胞扩散和解离局部粘连有关的残基聚集在BM-40的一个表面，与胶原蛋白和N-连接的碳水化合物的结合表位相反。延长的FS结构域在结构上与Kazal家族的丝氨酸蛋白酶抑制剂相关。显著的区别是插入了BM-40的抑制环，以及一个突出的N末端的β-发夹，与表皮生长因子有惊人的相似之处。这种发夹很可能在含有简单重复的FS结构域的蛋白质中起到刚性间隔区的作用，如卵泡抑素和集聚蛋白，并在卵泡抑素中形成肝素结合部位。
BM-40 (also known as SPARC or osteonectin) is an anti-adhesive secreted glycoprotein involved in tissue remodelling. Apart from an acidic N-terminal segment, BM-40 consists of a follistatin-like (FS) domain and an EF-hand calcium-binding (EC) domain. Here we report the crystal structure at 3.1 Angstrom resolution of the FS-EC domain pair of human BM-40, The two distinct domains interact through a small interface that involves the EF-hand pair of the EC domain. Residues implicated in cell binding, inhibition of cell spreading and disassembly of focal adhesions cluster on one face of BM-40, opposite the binding epitope for collagens and the N-linked carbohydrate. The elongated FS domain is structurally related to serine protease inhibitors of the Kazal family. Notable differences are an insertion into the inhibitory loop in BM-40 and a protruding N-terminal beta-hairpin with striking similarities to epidermal growth factor. This hairpin is likely to act as a rigid spacer in proteins containing tandemly repeated FS domains, such as follistatin and agrin, and forms the heparin-binding site in follistatin.