1apq: Difference between revisions

==Overview==

The calcium-dependent interaction between C1r and C1s, the two homologous, serine proteases of the first component of human complement C1, is, mediated by their N-terminal regions. The latter comprise an epidermal, growth factor (EGF)-like module exhibiting the consensus sequence, characteristic of Ca(2+)-binding EGF modules, surrounded by two CUB, modules. Due to its Ca2+ binding ability, the C1r EGF-like module, (C1r-EGF) is supposed to participate in the C1r-C1s interaction. An, additional interesting feature of C1r-EGF is the unusually large loop, connecting the first two conserved cysteine residues. The solution, structure of synthetic C1r-EGF (residues 123-175) has been determined, using nuclear magnetic resonance and combined simulated, annealing-restrained molecular dynamics calculations. The resulting family, of 19 structures is characterized by a well-ordered C-terminal part, (residues Cys 144-Ala174) with a backbone rmsd of 0.7 A and a disordered, N-terminal, including the large loop between the first two cysteines, (Cys129 and Cys144). This loop is known to be surface exposed and may be, expected to participate in domain-domain or protein-protein interactions., In its C-terminal part, C1r-EGF possesses the characteristic EGF fold with, a major and a minor beta-sheet. The latter comprises a beta-bulge, and, comparison with other EGF-like modules reveals the existence of two, distinct structural and sequential motifs in the bulged part. Additional, experiments in the presence of 80 mM Ca2+ did not show significant, structural variation of C1r-EGF, in keeping with previous observations on, blood-clotting factors IX and X.

==About this Structure==

[[Category: serine protease]]