PDBsum entry 3gau

Immune system

PDB id: 3gau

Contents

Protein chain

1213 a.a.* *

* Residue conservation analysis

* C-alpha coords only

PDB id:

3gau

Name:

Immune system

Title:

Solution structure of human complement factor h in 50 mm nacl buffer

Structure:

Complement factor h. Chain: a. Synonym: h factor 1

Source:

Homo sapiens. Human. Organism_taxid: 9606. Other_details: purified from pooled plasma

Ensemble:

8 models

Authors:

A.I.Okemefuna,R.Nan,J.Gor,S.J.Perkins

Key ref:

A.I.Okemefuna et al. (2009). Electrostatic interactions contribute to the folded-back conformation of wild type human factor H. J Mol Biol, 391, 98. PubMed id: 19505476

Date:

18-Feb-09 Release date: 09-Jun-09

Protein chain

P08603  (CFAH_HUMAN) -  Complement factor H from Homo sapiens

Seq: 1231 a.a.

Struc: 1213 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

J Mol Biol 391:98 (2009)

PubMed id: 19505476

Electrostatic interactions contribute to the folded-back conformation of wild type human factor H.

A.I.Okemefuna, R.Nan, J.Gor, S.J.Perkins.

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.