PDBsum entry 1w2r

Immune system

PDB id: 1w2r

Contents

Protein chain

142 a.a.* *

* Residue conservation analysis

* C-alpha coords only

PDB id:

1w2r

Name:

Immune system

Title:

Solution structure of cr2 scr 1-2 by x-ray scattering

Structure:

Complement receptor type 2 precursor,. Chain: a. Synonym: cr2 scr 1-2, complement c3d receptor, epstein-barr virus receptor, ebv receptor, cd21 antigen. Engineered: yes

Source:

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

Ensemble:

6 models

Authors:

H.E.Gilbert,J.P.Hannan,V.M.Holers,S.J.Perkins

Key ref:

H.E.Gilbert et al. (2005). Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study. J Mol Biol, 346, 859-873. PubMed id: 15713468 DOI: 10.1016/j.jmb.2004.12.006

Date:

08-Jul-04 Release date: 29-Sep-05

Protein chain

P20023  (CR2_HUMAN) -  Complement receptor type 2 from Homo sapiens

Seq: 1033 a.a.

Struc: 142 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/j.jmb.2004.12.006

J Mol Biol 346:859-873 (2005)

PubMed id: 15713468

Solution structure of the complex between CR2 SCR 1-2 and C3d of human complement: an X-ray scattering and sedimentation modelling study.

H.E.Gilbert, J.T.Eaton, J.P.Hannan, V.M.Holers, S.J.Perkins.

ABSTRACT

Complement receptor type 2 (CR2, CD21) forms a tight complex with C3d, a fragment of C3, the major complement component. Previous crystal structures of the C3d-CR2 SCR 1-2 complex and free CR2 SCR 1-2 showed that the two SCR domains of CR2 form contact with each other in a closed V-shaped structure. SCR 1 and SCR 2 are connected by an unusually long eight-residue linker peptide. Medium-resolution solution structures for CR2 SCR 1-2, C3d, and their complex were determined by X-ray scattering and analytical ultracentrifugation. CR2 SCR 1-2 is monomeric. For CR2 SCR 1-2, its radius of gyration R(G) of 2.12(+/-0.05) nm, its maximum length of 10nm and its sedimentation coefficient s20,w(o) of 1.40(+/-0.03) S do not agree with those calculated from the crystal structures, and instead suggest an open structure. Computer modelling of the CR2 SCR1-2 solution structure was based on the structural randomisation of the eight-residue linker peptide joining SCR 1 and SCR 2 to give 9950 trial models. Comparisons with the X-ray scattering curve indicated that the most favoured arrangements for the two SCR domains corresponded to an open V-shaped structure with no contacts between the SCR domains. For C3d, X-ray scattering and sedimentation velocity experiments showed that it exists as a monomer-dimer equilibrium with a dissociation constant of 40 microM. The X-ray scattering curve for monomeric C3d gave an R(G) value of 1.95 nm, and this together with its s20,w(o) value of 3.17 S gave good agreement with the monomeric C3d crystal structure. Modelling of the C3d dimer gave good agreements with its scattering and ultracentrifugation parameters. For the complex, scattering and ultracentrifugation experiments showed that there was no dimerisation, indicating that the C3d dimerisation site was located close to the CR2 SCR 1-2 binding site. The R(G) value of 2.44(+/-0.1) nm, its length of 9 nm and its s20,w(o) value of 3.45(+/-0.01) S showed that its structure was not much more elongated than that of C3d. Calculations with 9950 models of CR2 SCR 1-2 bound to C3d through SCR 2 showed that SCR 1 formed an open V-shaped structure with SCR 2 and was capable of interacting with the surface of C3d. We conclude that the open V-shaped structures formed by CR2 SCR 1-2, both when free and when bound to C3d, are optimal for the formation of a tight two-domain interaction with its ligand C3d.

Selected figure(s)

Figure 1.
Figure 1. Schematic diagrams of the CR2 SCR 1-2/C3d complex to show three alternative models for the complex comprising either (a) a compact V-shaped SCR structure, (b) an extended SCR structure, or (c) a folded-back SCR structure. The domains are drawn approximately to scale. The two SCR domains are joined by an eight residue linker (8) with their N terminus and C terminus denoted by N and C, respectively. Two potential N-linked glycosylation sites at Asn101 and Asn107 are shown by Y symbols. In this study, CR2 SCR 1-2 is deglycosylated, and only single GlcNAc residues are found at these two sites.

Figure 4.
Figure 4. X-ray distance distribution functions P(r) for CR2 SCR 1-2, C3d, and their complex. The maximum M of each P(r) curve shows the most frequently occurring distance within each molecule. The maximum dimension is denoted by L. (a) For CR2 SCR 1-2, M occurs at 2.1 nm and L at 10 nm. (b) For C3d, five different sample concentrations are shown at 0.5 mg ml -1 (red), 0.8 mg ml -1 (orange), 1.1 mg ml -1 (green), 2.1 mg ml -1 (blue), and 3.73 mg ml -1 (pink) from bottom to top. The three broken lines represent P(r) curves whose intensities have been increased by factors of 8.5 (0.5 mg ml -1), 7.0 (0.8 mg ml -1), and 5.5 (1.1 mg ml -1) for clarity. Peak M[1] corresponds to monomeric C3d and peak M[2] corresponds to its dimer. (c) For the complex, M occurs at 3.0 nm and L at 9 nm.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2005, 346, 859-873) copyright 2005.

Figures were selected by an automated process.