1APQ

STRUCTURE OF THE EGF-LIKE MODULE OF HUMAN C1R, NMR, 19 STRUCTURES

Summary for 1APQ

• Entry DOI: 10.2210/pdb1apq/pdb
• Descriptor: COMPLEMENT PROTEASE C1R (1 entity in total)
• Functional Keywords: complement, egf, calcium binding, serine protease
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 5984.46

Authors

Bersch, B.,Hernandez, J.-F.,Marion, D.,Arlaud, G.J. (deposition date: 1997-07-22, release date: 1997-09-17, Last modification date: 2024-11-13)

Primary citation

Bersch, B.,Hernandez, J.F.,Marion, D.,Arlaud, G.J.
Solution structure of the epidermal growth factor (EGF)-like module of human complement protease C1r, an atypical member of the EGF family.
Biochemistry, 37:1204-1214, 1998

PubMed Abstract: 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.

PubMed: 9477945
DOI: 10.1021/bi971851v

Experimental method

SOLUTION NMR