Molecular modelling of human complement component C3 and its fragments by solution scattering.
Solution scattering experiments using both X-rays and neutrons are reported for human complement component C3 and up to six other glycoprotein fragments that are derived from C3. The X-ray and neutron molecular masses and neutron matchpoints are in agreement with the known primary sequence of C3. The X-ray radius of gyration RG of C3 is 5.2 nm and is similar for the related forms C3u, C3(a + b) and C3b. The X-ray cross-sectional radius of gyration RXS of C3b is however less than that of C3, C3u and C3(a + b). The major fragments of C3b, namely C3c and C3dg, were studied. The RG of C3c is 4.7 nm and for C3dg is 2.9 nm. C3c and C3dg do not interact when they coexist in solution in equimolar amounts. When C3u is cleaved into iC3u, the RG of iC3u increases to 5.9 nm and its RXS decreases, showing that C3c and C3dg behave as independent entities within the parent glycoprotein. Analyses of the neutron RG and RXS values by contrast variation techniques confirm the X-ray analyses, and show no evidence for significant hydrophobic or hydrophilic domains within C3 or any of its fragments. Shape analyses show that C3, C3c and C3dg are elongated particles. Debye models were developed using the scattering curve out to Q = 1.6 nm-1. These show that C3 and C3c resemble oblate ellipsoids while C3dg resembles a prolate ellipsoid. C3dg lies on the long edge of C3c within C3. The dimensions of the models are 18 nm X 2 nm X 10 nm for C3, 18 nm X 2 nm X 7 nm for C3c and 10 nm X 2 nm X 3 nm for C3dg. These models are compatible with analyses of the scattering curve RG and RXS values, data from sedimentation coefficients, and images of C3 and C3c seen by electron microscopy.
D003176:Complement C3; D003179:Complement C3b; D015932:Complement C3c; D015933:Complement C3d; D006801:Humans; D008433:Mathematics; D008854:Microscopy, Electron; D008958:Models, Molecular; D009502:Neutrons; D010446:Peptide Fragments; D012542:Scattering, Radiation; D014965:X-Rays
D003176:Complement C3; D010446:Peptide Fragments; D003179:Complement C3b; D015932:Complement C3c; D015933:Complement C3d