Solution structures of complement components by X-ray and neutron scattering and analytical ultracentrifugation.
The short consensus/complement repeat (SCR) domain (also known as the complement control protein domain) is the most abundant domain type in the complement system. Crystal and NMR structures for proteins that contain single and multiple SCR domains have now been published. These contain inter-SCR linkers of between three and eight residues, and the structures show much variability in inter-SCR orientations. X-ray and neutron scattering, combined with analytical ultracentrifugation and constrained modelling based on known subunit structures will yield a medium-resolution structure for the protein of interest. The fewer parameters that are associated with the structure of interest, the more defined the structure of interest becomes. These solution studies have been applied to several SCR-containing proteins in the complement system, most notably Factor H with 20 SCR domains, a complement receptor type 2 fragment with two SCR domains, and rat complement receptor-related protein (Crry) which contains five SCR domains. The results show great conformational variability in the inter-SCR orientation, and these will be reviewed. Even though the rotational orientation cannot be modelled, it is nonetheless possible to measure the degree of extension of the multi-SCR proteins and, from this, to obtain functionally useful results.
Perkins
S J
SJ
Department of Biochemistry and Molecular Biology, Darwin Building, University College London, Gower Street, UK. s.perkins@rfc.ucl.ac.uk
Gilbert
H E
HE
Aslam
M
M
Hannan
J
J
Holers
V M
VM
Goodship
T H
TH
D000818:Animals; D003165:Complement System Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009502:Neutrons; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D051381:Rats; D012542:Scattering, Radiation; D013329:Structure-Activity Relationship; D014461:Ultracentrifugation / Q000379:methods*
D003165:Complement System Proteins; D003545:Cysteine