PDBsum entry 1ojv

Regulator of complement pathway

PDB id: 1ojv

Contents

Protein chain

254 a.a. *

Ligands

ACT ×3

SO4 ×2

GOL ×9

Waters ×212

* Residue conservation analysis

PDB id:

1ojv

Name:

Regulator of complement pathway

Title:

Decay accelerating factor (cd55): the structure of an intact human complement regulator.

Structure:

Complement decay-accelerating factor. Chain: a, b. Fragment: four extracellular scr domains residues 35-285. Synonym: cd55, daf. Engineered: yes. Other_details: modelled glycerols, acetates and sulphates from crystallisation buffer

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: human sequence expressed in e.Coli.

Biol. unit:

Dimer (from PDB file)

Resolution:

2.30Å R-factor: 0.210 R-free: 0.252

Authors:

P.Lukacik,P.Roversi,J.White,D.Esser,G.P.Smith,J.Billington, P.A.Williams,P.M.Rudd,M.R.Wormald,M.D.M.Crispin,C.M.Radcliffe, C.M.Dwek,D.J.Evans,B.P.Morgan,R.A.G.Smith,S.M.Lea

Key ref:

P.Lukacik et al. (2004). Complement regulation at the molecular level: the structure of decay-accelerating factor. Proc Natl Acad Sci U S A, 101, 1279-1284. PubMed id: 14734808 DOI: 10.1073/pnas.0307200101

Date:

16-Jul-03 Release date: 07-Jan-04

Protein chains

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

Seq: 381 a.a.

Struc: 254 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1073/pnas.0307200101

Proc Natl Acad Sci U S A 101:1279-1284 (2004)

PubMed id: 14734808

Complement regulation at the molecular level: the structure of decay-accelerating factor.

P.Lukacik, P.Roversi, J.White, D.Esser, G.P.Smith, J.Billington, P.A.Williams, P.M.Rudd, M.R.Wormald, D.J.Harvey, M.D.Crispin, C.M.Radcliffe, R.A.Dwek, D.J.Evans, B.P.Morgan, R.A.Smith, S.M.Lea.

ABSTRACT

The human complement regulator CD55 is a key molecule protecting self-cells from complement-mediated lysis. X-ray diffraction and analytical ultracentrifugation data reveal a rod-like arrangement of four short consensus repeat (SCR) domains in both the crystal and solution. The stalk linking the four SCR domains to the glycosylphosphatidylinositol anchor is extended by the addition of 11 highly charged O-glycans and positions the domains an estimated 177 A above the membrane. Mutation mapping and hydrophobic potential analysis suggest that the interaction with the convertase, and thus complement regulation, depends on the burial of a hydrophobic patch centered on the linker between SCR domains 2 and 3.

Selected figure(s)

Figure 1.
Fig. 1. Structure of CD55. (a) Structure of the four SCR domains (views at 0° and 90°). The molecule shown is molecule A from crystal form A (see Table 2). The structure is colored from blue at the N terminus to red at the C terminus. All figures were drawn with AESOP (M. E. M. Noble, unpublished program). (b) Comparison between eight copies of CD55[1234] from three different crystal forms. The molecules are overlaid with carbons from SCR domain 3 (residues 126-185) so that the lack of variation in the SCR 2/3 domain interface may be appreciated, and the molecules are colored so that the two copies from crystal forms A and B are red and green, respectively, and the four copies from crystal form C are blue. (c) Full model for CD55 in the cell membrane. This model combines the atomic coordinates for the SCR domains with models for the N- and O-linked sugars and the GPI anchor, built as described in the text. The molecule is embedded in a lipid monolayer to allow the extension of the stalk that supports the SCR domains above the membrane to be visualized.

Figure 3.
Fig. 3. Model of the complex between CD55 and the von Willebrand factor type A domain (vWF-A) of factor B. b and d show two views of the complex between CD55 and the vWF-A domain of factor B generated as described in the text. CD55 is oriented as in Fig. 1a Left. b shows a surface representation, and d shows a secondary structure trace for both molecules, which are colored as follows: CD55, the hydrophobic potential was calculated by using the program GRID and mapped onto the surface in AESOP (43) colored from green (most favorable for hydrophobic probe interaction) via yellow to white; and vWF-A of factor B, residues implicated in CD55 binding are colored red, and those implicated in C3b binding are colored orange; positions where mutation has no effect on CD55 sensitivity are colored blue. a and c show each molecule rotated 90° away from the view shown in b to allow inspection of the surfaces buried in the interface. CD55 is shown in the same view as in that of Fig. 1a Right.

Figures were selected by an automated process.