Crystal structure of the bovine lactadherin C2 domain, a membrane binding motif, shows similarity to the C2 domains of factor V and factor VIII
Crystal structure of the bovine lactadherin C2 domain, a membrane binding motif, shows similarity to the C2 domains of factor V and factor VIII
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DOI：
10.1016/j.jmb.2007.05.054
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发表时间：
2007-08-17
影响因子：
5.6
通讯作者：
Furie, Barbara C.
中科院分区：
文献类型：
--
作者：
Lin, Lin;Huai, Oing;Furie, Barbara C.
乳粘附素是一种由多种细胞分泌的糖蛋白，含有两个EGF结构域和两个C结构域，与凝血蛋白因子V和因子VIII的C结构域序列具有同源性。与这些蛋白一样，乳粘附素以高亲和力结合到含有磷脂酰丝氨酸(PS)的膜上。我们在2.4埃测定了牛乳胶粘附素C2结构域(残基1到158)的晶体结构。乳粘附素C2结构类似于因子V和的C2结构域(C-α原子的均方根密度分别为0.9埃和1.2埃，序列同源性分别为43%和38%)。乳粘附素C2结构域有一个盘状折叠，包含两个由五条和三条反平行的β链组成的相互堆积的β-链。N和C末端通过二硫键连接在Cys1和Cys158之间。一个β-转角和两个包含溶剂暴露的疏水残基的环从C2结构域的β-夹心核心延伸。与因子V和VIII的C2结构域类似，这些暴露在溶剂中的疏水残基Trp26、Leu28、Phe31和Phe81中的一些或全部可能参与膜结合。乳胶粘附素的C2结构域可作为细胞表面磷脂酰丝氨酸暴露的标志，并可能作为一种独特的抗血栓药物。(C)2007爱思唯尔有限公司。保留所有权利。
Lactadherin, a glycoprotein secreted by a variety of cell types, contains two EGF domains and two C domains with sequence homology to the C domains of blood coagulation proteins factor V and factor VIII. Like these proteins, lactadherin binds to phosphatidylserine (PS)-containing membranes with high affinity. We determined the crystal structure of the bovine lactadherin C2 domain (residues 1 to 158) at 2.4 angstrom. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C-alpha atoms of 0.9 angstrom and 1.2 angstrom, and sequence identities of 43% and 38%, respectively). The lactadherin C2 domain has a discoidin-like fold containing two beta-sheets of five and three antiparallel beta-strands packed against one another. The N and C termini are linked by a disulfide bridge between Cys1 and Cys158. One beta-turn and two loops containing solvent-exposed hydrophobic residues extend from the C2 domain beta-sandwich core. In analogy with the C2 domains of factors V and VIII, some or all of these solvent-exposed hydrophobic residues, Trp26, Leu28, Phe31, and Phe81, likely participate in membrane binding. The C2 domain of lactadherin may serve as a marker of cell surface phosphatidylserine exposure and may have potential as a unique anti-thrombotic agent. (c) 2007 Elsevier Ltd. All rights reserved.