PDBsum entry 1h2q

Immune system protein

PDB id: 1h2q

Contents

Protein chain

119 a.a. *

* Residue conservation analysis

PDB id:

1h2q

Name:

Immune system protein

Title:

Human cd55 domains 3 & 4

Structure:

Complement decay-accelerating factor. Chain: p. Fragment: extracellular scr domains 3 & 4, residues 161-285. Synonym: cd55 antigen, cd55, daf. Engineered: yes

Source:

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

Resolution:

3.00Å R-factor: 0.263 R-free: 0.319

Authors:

P.Williams,Y.Chaudhry,I.G.Goodfellow,J.Billington,R.Powell, O.B.Spiller,D.J.Evans,S.M.Lea

Key ref:

P.Williams et al. (2003). Mapping CD55 function. The structure of two pathogen-binding domains at 1.7 A. J Biol Chem, 278, 10691-10696. PubMed id: 12499389 DOI: 10.1074/jbc.M212561200

Date:

13-Aug-02 Release date: 25-Sep-03

Protein chain

P08174  (DAF_HUMAN) -  Complement decay-accelerating factor from Homo sapiens

Seq: 381 a.a.

Struc: 119 a.a.

DOI no: 10.1074/jbc.M212561200

J Biol Chem 278:10691-10696 (2003)

PubMed id: 12499389

Mapping CD55 function. The structure of two pathogen-binding domains at 1.7 A.

P.Williams, Y.Chaudhry, I.G.Goodfellow, J.Billington, R.Powell, O.B.Spiller, D.J.Evans, S.Lea.

ABSTRACT

Decay-accelerating factor (CD55), a regulator of the alternative and classical pathways of complement activation, is expressed on all serum-exposed cells. It is used by pathogens, including many enteroviruses and uropathogenic Escherichia coli, as a receptor prior to infection. We describe the x-ray structure of a pathogen-binding fragment of human CD55 at 1.7 A resolution containing two of the three domains required for regulation of human complement. We have used mutagenesis to map biological functions onto the molecule; decay-accelerating activity maps to a single face of the molecule, whereas bacterial and viral pathogens recognize a variety of different sites on CD55.

Selected figure(s)

Figure 1.
Fig. 1. Fold and arrangement of SCR domains in CD55[34]. This figure was drawn using AESOP (M. E. M. Noble, unpublished program). A, secondary structure and location of disulfide bonds in CD55[34]. Strands are labeled according to the convention defined by Norman et al. (35). Note that there is no strand 1 as the hydrogen-bonding pattern of these residues does not meet the strict criteria for definition of a -strand. B, variation in orientation between SCR domains 3 and 4 in the five independent copies of CD55[34] found in the different crystal forms (Table I). C, model for topology of CD55 in the membrane based on our structure of CD55[34].

Figure 3.
Fig. 3. Mapping of functional data onto the structure of CD55[34]. This figure was drawn using AESOP (M. E. M. Noble, unpublished program). All plates show two views of the surface of CD55, the first view corresponding to the orientation as shown in Fig. 1 and termed Front View. The Back View corresponds to a rotation of 180 degrees about the long axis of the molecule. A, orange indicates the sites mutagenized in this study, and yellow indicates the sites of sequence difference between AGM and human CD55. B, AP indicates the mutation shown to effect alternative pathway decay acceleration, and CP indicates those sites shown to affect classical pathway decay acceleration; both those sites have been shown to affect both pathways. Dark green indicates those sites shown previously to effect both classical and alternative pathway decay acceleration (22). C, sites marked with a virus name have been shown to affect binding of that virus. Sites marked in pale pink are the sites of difference between AGM and human CD55 that are known to abolish EV11 binding and significantly reduce EV12 binding. D, the locations of two of the Cromer variants of human CD55 are shown. Different E. coli strains are sensitive to changes at one or other of these positions (28, 30, 32).

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 10691-10696) copyright 2003.

Figures were selected by an automated process.