1nzi

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spinqualitylabelsall models 1nzi, resolution 1.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of the CUB1-EGF Interaction Domain of Complement Protease C1s

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

C1, the complex that triggers the classical pathway of complement, is, assembled from two modular proteases C1r and C1s and a recognition protein, C1q. The N-terminal CUB1-EGF segments of C1r and C1s are key elements of, the C1 architecture, because they mediate both Ca2+-dependent C1r-C1s, association and interaction with C1q. The crystal structure of the, interaction domain of C1s has been solved and refined to 1.5 A resolution., The structure reveals a head-to-tail homodimer involving interactions, between the CUB1 module of one monomer and the epidermal growth factor, (EGF) module of its counterpart. A Ca2+ ion is bound to each EGF module, and stabilizes both the intra- and inter-monomer interfaces. Unexpectedly, a second Ca2+ ion is bound to the distal end of each CUB1 module, through, six ligands contributed by Glu45, Asp53, Asp98, and two water molecules., These acidic residues and Tyr17 are conserved in approximately two-thirds, of the CUB repertoire and define a novel, Ca2+-binding CUB module subset., The C1s structure was used to build a model of the C1r-C1s CUB1-EGF, heterodimer, which in C1 connects C1r to C1s and mediates interaction with, C1q. A structural model of the C1q/C1r/C1s interface is proposed, where, the rod-like collagen triple helix of C1q is accommodated into a groove, along the transversal axis of the C1r-C1s heterodimer.

Disease

Known diseases associated with this structure: C1r/C1s deficiency, combined OMIM:[120580], C1s deficiency, isolated OMIM:[120580]

About this Structure

1NZI is a Single protein structure of sequence from Homo sapiens with CA and MG as ligands. Active as Complement subcomponent C1s, with EC number 3.4.21.42 Full crystallographic information is available from OCA.

Reference

X-ray structure of the Ca2+-binding interaction domain of C1s. Insights into the assembly of the C1 complex of complement., Gregory LA, Thielens NM, Arlaud GJ, Fontecilla-Camps JC, Gaboriaud C, J Biol Chem. 2003 Aug 22;278(34):32157-64. Epub 2003 Jun 4. PMID:12788922

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