2PQS

Crystal Structure of the Bovine Lactadherin C2 Domain

Summary for 2PQS

• Entry DOI: 10.2210/pdb2pqs/pdb
• Descriptor: Lactadherin (2 entities in total)
• Functional Keywords: c2 domain, lactadherin, membrane binding, cell adhesion
• Biological source: Bos taurus (cattle)
• Cellular location: Membrane; Peripheral membrane protein: Q95114
• Total number of polymer chains: 4
• Total formula weight: 72380.93

Authors

Huang, M.,Furie, B.C. (deposition date: 2007-05-02, release date: 2007-08-07, Last modification date: 2011-07-13)

Primary citation

Lin, L.,Huai, Q.,Huang, M.,Furie, B.,Furie, B.C.
Crystal structure of the bovine lactadherin C2 domain, a membrane binding motif, shows similarity to the C2 domains of factor V and factor VIII.
J.Mol.Biol., 371:717-724, 2007

PubMed Abstract: 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 A. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C(alpha) atoms of 0.9 A and 1.2 A, 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.

PubMed: 17583728
DOI: 10.1016/j.jmb.2007.05.054

Experimental method

X-RAY DIFFRACTION (2.4 Å)