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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• 作者：Lin Lin ; Qing Huai ; Mingdong Huang ; Bruce Furie ; Barbara C. Furie
• 关键词：crystal structure ; C2 domain ; lactadherin ; factor V ; factor VIII
• 刊名：Journal of Molecular Biology
• 出版年：2007
• 出版时间：17 August 2007
• 年：2007
• 卷：371
• 期：3
• 页码：717-724
• 全文大小：1194 K

文摘

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 Å. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C_α atoms of 0.9 Å and 1.2 Å, and sequence identities of 43 % and 38 % , respectively). The lactadherin C2 domain has a discoidin-like fold containing two β-sheets of five and three antiparallel β-strands packed against one another. The N and C termini are linked by a disulfide bridge between Cys1 and Cys158. One β-turn and two loops containing solvent-exposed hydrophobic residues extend from the C2 domain β-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.