2ATY

Complement receptor chimaeric conjugate CR2-Ig

Summary for 2ATY

• Entry DOI: 10.2210/pdb2aty/pdb
• Related: 1GHQ 1IGY 1W2R
• Descriptor: Complement receptor chimeric conjugate CR2-Ig (1 entity in total)
• Functional Keywords: immunoglobulin fold, antibody, complement, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 83997.20

Authors

Gilbert, H.E.,Aslam, M.,Guthridge, J.M.,Holers, V.M.,Perkins, S.J. (deposition date: 2005-08-26, release date: 2006-01-31, Last modification date: 2024-02-14)

Primary citation

Gilbert, H.E.,Aslam, M.,Guthridge, J.M.,Holers, V.M.,Perkins, S.J.
Extended Flexible Linker Structures in the Complement Chimaeric Conjugate CR2-Ig by Scattering, Analytical Ultracentrifugation and Constrained Modelling: Implications for Function and Therapy.
J.Mol.Biol., 356:397-412, 2006

PubMed Abstract: Complement receptor 2 (CR2; CD21) is a membrane-bound regulator of complement activation, being comprised of 15 or 16 short complement repeat (SCR) domains. A recombinant glycosylated human CR2 SCR 1-2 domain pair was engineered with the Fc fragment of a mouse IgG1 antibody to create a chimaera CR2-Ig containing the major ligand binding domains. Such a chimaera has therapeutic potential as a complement inhibitor or immune modulator. X-ray and neutron scattering and analytical ultracentrifugation identified its domain structure in solution, and provided a comparison with controversial folded-back crystal structures for deglycosylated CR2 SCR 1-2. The radius of gyration R(G) of CR2-Ig was determined to be 5.39(+/-0.14) nm and 5.29(+/-0.01) nm by X-ray and neutron scattering, respectively. The maximum dimension of CR2-Ig was determined to be 17 nm. The molecular mass of CR2-Ig ranged between 101,000 Da and 107,000 Da as determined by neutron scattering and sedimentation equilibrium, in good agreement with the sequence-derived value of 106,600 Da. Sedimentation velocity gave a sedimentation coefficient of 4.49(+/-0.11) S. Stereochemically complete models for CR2-Ig were constructed from crystal structures for the CR2 SCR 1-2 and mouse IgG1 Fc fragments. The two SCR domains and the Fc fragment were joined by randomised conformational peptides. The analysis of 35,000 possible CR2-Ig models showed that only those models in which the two SCR domains were arranged in an open V-shape in random orientations about the Fc fragment accounted for the scattering and sedimentation data. It was not possible to define one single conformational family of Fab-like fragment relative to the Fc fragment. This flexibility is attributed to the relatively long linker sequence and the absence of the antibody light chain from CR2-Ig. The modelling also confirmed that the structure of CR2 SCR 1-2 is more extended in solution than in its crystal structure.

PubMed: 16375923
DOI: 10.1016/j.jmb.2005.11.050

Experimental method

SOLUTION SCATTERING