1ppq

From Proteopedia

Revision as of 11:27, 20 March 2008

NMR structure of 16th module of Immune Adherence Receptor, Cr1 (Cd35)

Overview

The regulators of complement activation (RCA) are critical to health and disease because their role is to ensure that a complement-mediated immune response to infection is proportionate and targeted. Each protein contains an uninterrupted array of from four to 30 examples of the very widely occurring complement control protein (CCP, or sushi) module. The CCP modules mediate specific protein-protein and protein-carbohydrate interactions that are key to the biological function of the RCA and, paradoxically, provide binding sites for numerous pathogens. Although structural and mutagenesis studies of CCP modules have addressed some aspects of molecular recognition, there have been no studies of the role of molecular dynamics in the interaction of CCP modules with their binding partners. NMR has now been used in the first full characterization of the backbone dynamics of CCP modules. The dynamics of two individual modules-the 16th of the 30 modules of complement receptor type 1 (CD35), and the N-terminal module of membrane cofactor protein (CD46)-as well as their solution structures, are compared. Although both examples share broadly similar three-dimensional structures, many structurally equivalent residues exhibit different amplitudes and timescales of local backbone motion. In each case, however, regions of the module-surface implicated by mutagenesis as sites of interactions with other proteins include several mobile residues. This observation suggests further experiments to explore binding mechanisms and identify new binding sites.

Disease

Known diseases associated with this structure: Blood group, Knops system OMIM:[120620], CR1 deficiency OMIM:[120620], Malaria, severe, resistance to OMIM:[120620], SLE susceptibility OMIM:[120620]

About this Structure

1PPQ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Backbone dynamics of complement control protein (CCP) modules reveals mobility in binding surfaces., O'Leary JM, Bromek K, Black GM, Uhrinova S, Schmitz C, Wang X, Krych M, Atkinson JP, Uhrin D, Barlow PN, Protein Sci. 2004 May;13(5):1238-50. PMID:15096630

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