PDBsum entry 3kzj

Immune system

PDB id

3kzj

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Contents

			Protein chain

					125 a.a. *

			Ligands

					SO4 ×2

			Waters ×297

* Residue conservation analysis

PDB id:

3kzj

Links

Name:

Immune system

Title:

Structure of complement factor h variant r1203a

Structure:

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

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Resolution:

1.65Å

R-factor:

0.204

R-free:

0.222

Authors:

A.Bhattacharjee,M.J.Lehtinen,T.Kajander,A.Goldman,T.S.Jokiranta

Key ref:

A.Bhattacharjee et al. (2010). Both domain 19 and domain 20 of factor H are involved in binding to complement C3b and C3d. Mol Immunol, 47, 1686-1691. PubMed id: 20378178

Date:

08-Dec-09

Release date:

19-May-10

PROCHECK

	Headers

	References

Protein chain

P08603 (CFAH_HUMAN) - Complement factor H from Homo sapiens

Seq: Struc:

Seq: Struc:

Seq: Struc:					1231 a.a. 125 a.a.*

Key:

PfamA domain

Secondary structure

CATH domain

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

	Mol Immunol 47:1686-1691 (2010)
PubMed id: 20378178

Both domain 19 and domain 20 of factor H are involved in binding to complement C3b and C3d.
A.Bhattacharjee, M.J.Lehtinen, T.Kajander, A.Goldman, T.S.Jokiranta.

ABSTRACT

Factor H (FH) regulates the alternative pathway of complement in plasma and mediates discrimination of cellular surfaces to alternative pathway activators and non-activators. The carboxyl-terminal domains 19 and 20 of FH are essential in target discrimination and are known to contain binding sites for the C3d part of C3b, heparin, and endothelial cells. Mutations in FH19-20 are frequently found in patients with atypical haemolytic uremic syndrome (aHUS). Most aHUS-associated and some other mutations have been shown to lead to impaired binding to C3d and C3b by the recombinant FH19-20 fragment. Most of these mutated residues, such as R1203, are located close to each other in domain 20 but some, such as Q1139, are located in domain 19. We generated mutant proteins Q1139A and R1203A of FH19-20 and showed that their binding to C3d and C3b was clearly impaired. To show that the effects on C3d/C3b binding are due to direct interactions rather than structural changes, we solved the X-ray crystal structures of the R1203A and Q1139A mutant proteins at 1.65 and 2.0A, respectively. Neither of the mutations caused any overall structural changes in FH19-20. It is thus evident that Q1139 in domain 19 and R1203 in domain 20 are directly involved in binding to the C3d part of C3b and therefore both the domains are involved in the interaction with C3d and C3b. This explains why several aHUS-associated FH mutations are found within domain 19 in addition to domain 20.

Literature references that cite this PDB file's key reference

PubMed id

Reference

21317894

H.P.Morgan, C.Q.Schmidt, M.Guariento, B.S.Blaum, D.Gillespie, A.P.Herbert, D.Kavanagh, H.D.Mertens, D.I.Svergun, C.M.Johansson, D.Uhrín, P.N.Barlow, and J.P.Hannan (2011).
Structural basis for engagement by complement factor H of C3b on a self surface.

Nat Struct Mol Biol, 18, 463-470.

PDB code:

3oxu

21285368

T.Kajander, M.J.Lehtinen, S.Hyvärinen, A.Bhattacharjee, E.Leung, D.E.Isenman, S.Meri, A.Goldman, and T.S.Jokiranta (2011).
Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement.

Proc Natl Acad Sci U S A, 108, 2897-2902.

PDB code:

2xqw

The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.