¹H, ¹³C and ¹⁵N resonance assignments of the complement control protein modules of the complement component C7
Carla Clark1, Chuong-Thu Thai, Marie M Phelan
1Edinburgh Biomolecular NMR Unit, Joseph Black Building, University of Edinburgh, West Mains Road, Edinburgh EH9 3JJ, Scotland, UK.
Insights
Researchers determined the structure of human complement C7 complement control protein modules (CCPs). These findings provide insights into the assembly of the membrane attack complex (MAC) and its role in the complement system.
Area of Science:
- Biochemistry
- Immunology
- Structural Biology
Background:
- Human complement protein C7 is crucial for forming the membrane attack complex (MAC).
- C7 contains complement control protein (CCP) modules and Factor-I like (FIM) modules.
- The CCP modules are hypothesized to facilitate C7's binding to C5b.
Purpose of the Study:
- To elucidate the structure of the C7-CCPs.
- To provide NMR chemical shift assignments for the C7-CCPs.
Main Methods:
- Production of a 14-kDa recombinant C7-CCPs protein.
- Utilized triple-resonance Nuclear Magnetic Resonance (NMR) spectroscopy.
- Collected backbone and side-chain NMR chemical shift assignments.
Main Results:
- Achieved 98% backbone and 94% side-chain NMR assignments for C7-CCPs.
- NMR chemical shifts and assignments were deposited in the BioMagResBank (accession 18530).
Conclusions:
- The study provides foundational structural data for the C7-CCPs.
- These assignments are critical for understanding C7's role in MAC formation and complement-mediated immunity.
Abstract:
Human C7 is one of four homologous complement proteins that self-assemble on the nascent activation-specific fragment, C5b, thus forming the cytolytic membrane attack complex (MAC). In addition to the conserved modular core of the MAC/perforin protein family, C7 has four C-terminal domains comprising a pair of complement control protein modules (CCPs) preceding two Factor-I like modules (FIMs). It is proposed that the C7-CCPs might serve as a molecular arm for delivery of C7-FIMs to their binding site on C5b. Here we present the NMR chemical shift assignments for the C7-CCPs produced as a 14-kDa recombinant protein. Based upon triple-resonance experiments, 98 and 94 % of the backbone and side-chain ((1)H, (13)C and (15)N) assignments, respectively, have been completed. The chemical shifts and assignments have been deposited in the BioMagResBank database under accession number 18530.
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