3GAU: Solution structure of Human Complement Factor H in 50 mM NaCl buffer

Citation:
Abstract
Factor H (FH), a major serum regulator of C3b in the complement alternative pathway, is composed of 20 short complement regulator (SCR) domains. Earlier solution structures for FH showed that this has a folded-back domain arrangement and exists as oligomers. To clarify the molecular basis for this, analytical ultracentrifugation and X-ray scattering studies of native FH were performed as a function of NaCl concentration and pH. The sedimentation coefficient for the FH monomer decreased from 5.7 S to 5.3 S with increase in NaCl concentration, showing that weak electrostatic inter-domain interactions affect its folded-back structure. FH became more elongated at pH 9.4, showing the involvement of histidine residue(s) in its folded-back structure. Similar studies of partially deglycosylated FH suggested that oligosaccharides were not significant in determining the FH domain structure. The formation of FH oligomers decreased with increased NaCl concentration, indicating that electrostatic interactions also affect this. X-ray scattering showed that the maximum length of FH increased from 32 nm in low salt to 38 nm in high salt. Constrained X-ray scattering modelling was used to generate significantly improved FH molecular structures at medium resolution. In 50 mM NaCl, the modelled structures showed that inter-SCR domain contacts are likely, while these contacts are fewer in 250 mM NaCl. The results of this study show that the conformation of FH is affected by its local environment, and this may be important for its interactions with C3b and when bound to polyanionic cell surfaces.
PDB ID: 3GAUDownload
MMDB ID: 73165
PDB Deposition Date: 2009/2/18
Updated in MMDB: 2017/11
Experimental Method:
solution scattering
Source Organism:
Similar Structures:
Biological Unit for 3GAU: monomeric; determined by author
Molecular Components in 3GAU
Label Count Molecule
Protein (1 molecule)
1
Complement Factor H(Gene symbol: CFH)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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