2aty

OverviewOverview

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.

About this StructureAbout this Structure

2ATY is a Single protein structure of sequence from Homo sapiens, mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

Extended flexible linker structures in the complement chimaeric conjugate CR2-Ig by scattering, analytical ultracentrifugation and constrained modelling: implications for function and therapy., Gilbert HE, Aslam M, Guthridge JM, Holers VM, Perkins SJ, J Mol Biol. 2006 Feb 17;356(2):397-412. Epub 2005 Dec 5. PMID:16375923

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