PDBsum entry 2g7i

Immune system

PDB id: 2g7i

Contents

Protein chain

124 a.a. *

Waters ×177

* Residue conservation analysis

PDB id:

2g7i

Name:

Immune system

Title:

Structure of human complement factor h carboxyl terminal domains 19- 20: a basis for atypical hemolytic uremic syndrome

Structure:

Complement factor h. Chain: a. Fragment: c-terminal domains 19-20. Synonym: h factor 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cfh, hf, hf1. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Biol. unit:

Tetramer (from PDB file)

Resolution:

1.75Å R-factor: 0.207 R-free: 0.225

Authors:

V.-P.Jaakola,T.S.Jokiranta,A.Goldman

Key ref:

T.S.Jokiranta et al. (2006). Structure of complement factor H carboxyl-terminus reveals molecular basis of atypical haemolytic uremic syndrome. EMBO J, 25, 1784-1794. PubMed id: 16601698 DOI: 10.1038/sj.emboj.7601052

Date:

28-Feb-06 Release date: 23-May-06

Protein chain

P08603  (CFAH_HUMAN) -  Complement factor H from Homo sapiens

Seq: 1231 a.a.

Struc: 124 a.a.

DOI no: 10.1038/sj.emboj.7601052

EMBO J 25:1784-1794 (2006)

PubMed id: 16601698

Structure of complement factor H carboxyl-terminus reveals molecular basis of atypical haemolytic uremic syndrome.

T.S.Jokiranta, V.P.Jaakola, M.J.Lehtinen, M.Pärepalo, S.Meri, A.Goldman.

ABSTRACT

Factor H (FH) is the key regulator of the alternative pathway of complement. The carboxyl-terminal domains 19-20 of FH interact with the major opsonin C3b, glycosaminoglycans, and endothelial cells. Mutations within this area are associated with atypical haemolytic uremic syndrome (aHUS), a disease characterized by damage to endothelial cells, erythrocytes, and kidney glomeruli. The structure of recombinant FH19-20, solved at 1.8 A by X-ray crystallography, reveals that the short consensus repeat domain 20 contains, unusually, a short alpha-helix, and a patch of basic residues at its base. Most aHUS-associated mutations either destabilize the structure or cluster in a unique region on the surface of FH20. This region is close to, but distinct from, the primary heparin-binding patch of basic residues. By mutating five residues in this region, we show that it is involved, not in heparin, but in C3b binding. Therefore, the majority of the aHUS-associated mutations on the surface of FH19-20 interfere with the interaction between FH and C3b. This obviously leads to impaired control of complement attack on plasma-exposed cell surfaces in aHUS.

Selected figure(s)

Figure 1.
Figure 1 Electrostatic potential of FH19–20 on the surface in two views 90° apart. Positive surface is blue and negative red.

Figure 2.
Figure 2 Tetrameric assembly of FH19–20, in stereo view. Each of the monomers is in a different colour. The B and C monomer amino-termini are on top (blue and purple), while the A and D amino-termini are at the bottom (red and green). A schematic view from the top is shown.

The above figures are reprinted by permission from Macmillan Publishers Ltd: EMBO J (2006, 25, 1784-1794) copyright 2006.

Figures were selected by an automated process.