Solution structures of complement components by X-ray and neutron scattering and analytical ultracentrifugation
S J Perkins1, H E Gilbert, M Aslam
1Department of Biochemistry and Molecular Biology, Darwin Building, University College London, Gower Street, UK. s.perkins@rfc.ucl.ac.uk
Biochemical Society Transactions
|November 21, 2002
Summary
The short consensus repeat (SCR) domain is abundant in the complement system. Studies reveal significant conformational variability in multi-SCR proteins, offering functionally useful insights despite rotational orientation limitations.
Area of Science:
- Biochemistry
- Structural Biology
- Immunology
Background:
- The short consensus/complement repeat (SCR) domain, also known as the complement control protein domain, is a prevalent structural motif within the complement system.
- Published crystal and NMR structures reveal inter-SCR linkers ranging from three to eight residues, exhibiting considerable variability in inter-domain orientations.
Purpose of the Study:
- To investigate the structural variability and conformational dynamics of multi-SCR proteins within the complement system.
- To apply solution scattering and modeling techniques to determine medium-resolution structures of SCR-containing proteins.
Main Methods:
- Utilized X-ray and neutron scattering techniques.
- Employed analytical ultracentrifugation.
- Incorporated constrained modeling based on known subunit structures.
- Applied these methods to Factor H, complement receptor type 2 fragment, and rat complement receptor-related protein (Crry).
Main Results:
- Demonstrated significant conformational variability in the orientation of SCR domains within multi-domain proteins.
- Observed that while rotational orientation is not precisely modeled, the degree of extension can be measured.
- These findings provide functionally relevant data on the structural flexibility of SCR proteins.
Conclusions:
- Multi-SCR proteins in the complement system exhibit substantial conformational flexibility.
- Solution-based structural studies, even without precise rotational modeling, yield valuable functional insights into these dynamic protein structures.
