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Persistent URL http://purl.org/net/epubs/work/64620
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Record Id 64620
Title Demonstration by pulsed neutron scattering that the arrangement of the Fab and Fc fragments in the overall structures of bovine IgGi and IgG2 in solution is similar
Abstract The bovine IgGI and IgG2 isotypes exhibit large differences in effector functions. To examine the structural basis for this, the 12-domain structures of IgGI and IgG2 were investigated by pulsed neutron scattering using a recently developed camera LOQ. This method reports on the average relative disposition in solution of the Fab and Fc fragments in IgG. The radii of gyration (RG) were found to be similar at 5.64 and 5.71 nm for IgGI and IgG2 respectively in 100% 2H20 buffers. The two cross-sectional radii of gyration (RXS) were also similar at 2.38-2.41 and 0.98-1.02 nm. Similar values were obtained for porcine IgG. Both bovine IgGI and IgG2 possess similar overall solution structures, despite sequence differences at the hinge region at the centre of their structures. An automated computer survey of possible IgG structures was developed, in which coordinates for the two Fab fragments were displaced in a twodimensional plane relative to those of the Fc fragment in 0.25 nm steps. The scattering curves calculated from these structures were found to be sensitive to relative displacements of the three fragments, but not on their rotational orientation about their longest axes. Good agreement with the solution scattering data was obtained with a planar IgG model in which the C-terminus of the CHI domain of Fab was 3.6 nm from the N-terminus of Fc in both IgGI and IgG2, with a precision of 0.7 nm. Energy refinement showed that this spatial separation is compatible with the hinge sequences of bovine IgGi and IgG2. The results show that multidomain protein structures can be modelled using LOQ data, and that a long hinge sequence does not necessarily reflect a large distance between Fab and Fc. The steric accessibility of Fc sites for interactions with cell-surface Fc receptors and Cl q of complement is shown to be generally similar for IgGI and IgG2, and the difference in effector function between IgGI and IgG2 is probably based on deletions in the IgG2 hinge sequence.
Organisation CCLRC , ISIS , ISIS-LOQ
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Language English (EN)
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Journal Article Biochem J 311, no. 1 (1995): 283-291. doi:10.1042/bj3110283 1995