Molecular modeling of human complement component C4 and its fragments by X-ray and neutron solution scattering

Journal Article · Tue Feb 06 04:00:00 EST 1990 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00457a011· OSTI ID:6828388

Perkins, S J; Nealis, A S; Sim, R B ^[1]

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1. Royal Free Hospital School of Medicine, London (England)

The solution structures of human complement component C4 and five derived fragments, C4u, C4(a + b), C4b, C4c, and C4d, were analyzed by synchrotron X-ray and neutron scattering. The X-ray radii of gyration RG for C4, C4u, and C4(a + b) in H2O buffers are similar at 5.23-5.28 nm. Molecular mass calculations using X-rays and neutrons show unexpectedly that C4c is dimeric; however, all the other forms are monomeric. C4c2 has an X-ray RG of 5.18 nm and an RXS of 2.89 nm. Neutron contrast variation gives RG values at infinite contrast of 4.87-4.93 nm for C4 and C4u, 4.79 nm for C4b, 4.94 nm for C4c2, and 2.69 nm for C4d. The RXS values at infinite contrast are 2.23-2.25 nm for C4 and C4u, 1.89 nm for C4b, and 2.62 nm for C4c2. These data show that a large conformational change occurs on going from C4 to C4b, but not on going from C4 to C4u, and this is attributed to the presence of the C4a moiety in C4u. Comparisons of the C4 and C4u scattering curves show that these are very similar out to a nominal resolution of 4 nm. Scattering-curve models were developed to account for the neutron scattering curves of C4, C4c2, and C4d in 2H2O buffers. The C4c monomer could be represented by a lamellar ellipsoid of size 8 nm x 2 nm x 18 nm. C4d was found to be 4 nm x 2 nm x 9 nm. The combination of these structures gave good accounts of the neutron data for C4, C4b, and C4c2 to resolutions of 5-6 nm. The C4 model was obtained by placing the long axis of C4d parallel to that of C4c such that the cross section is extended. C4b was best modeled by repositioning C4d relative to C4c such that this cross section becomes more compact. The C4 and C4b models are compared with possible structures for the C1 component of complement to show the importance of the surface accessibility of the protease domains and short consensus repeat domains in C1 for C4 activation.

• OSTI ID: 6828388
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 29:5; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
BARYONS
CHEMICAL ANALYSIS
COMPLEMENT
DEUTERIUM
ELECTROMAGNETIC RADIATION
ELECTRON MICROPROBE ANALYSIS
ELEMENTARY PARTICLES
FERMIONS
HADRONS
HYDROGEN COMPOUNDS
HYDROGEN ISOTOPES
IONIZING RADIATIONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
MAMMALS
MAN
MICROANALYSIS
MOLECULAR STRUCTURE
NEUTRONS
NUCLEI
NUCLEONS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PRIMATES
PROTEINS
RADIATIONS
SCATTERING
STABLE ISOTOPES
TRACER TECHNIQUES
VERTEBRATES
WATER
X RADIATION