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Large-scale modelling as a route to multiple surface comparisons of the CCP module family

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)379-88
Number of pages10
JournalProtein engineering, design & selection : PEDS
Volume18
Issue number8
DOIs
Publication statusPublished - 2005

Abstract

Numerous mammalian proteins are constructed from a limited repertoire of module-types. Proteins belonging to the regulators of complement activation family--crucial for ensuring a complement-mediated immune response is targeted against infectious agents--are composed solely of complement control protein (CCP) modules. In the current study, CCP module sequences were grouped to allow selection of the most appropriate experimentally determined structures to serve as templates in an automated large-scale structure modelling procedure. The resulting 135 individual CCP module models, valuable in their own right, are available at the online database http://www.bru.ed.ac.uk/~dinesh/ccp-db.html. Comparisons of surface properties within a particular family of modules should be more informative than sequence alignments alone. A comparison of surface electrostatic features was undertaken for the first 28 CCP modules of complement receptor type 1 (CR1). Assignments to clusters based on surface properties differ from assignments to clusters based on sequences. This observation might reflect adaptive evolution of surface-exposed residues involved in protein-protein interactions. This illustrative example of a multiple surface-comparison was indeed able to pinpoint functional sites in CR1.

    Research areas

  • Amino Acid Sequence, Animals, Databases, Protein, Humans, Models, Molecular, Protein Structure, Tertiary, Receptors, Complement, Sequence Alignment, Static Electricity, Structural Homology, Protein

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