2i24
Crystal structure analysis of the nurse shark New Antigen Receptor PBLA8 variable domain
OverviewOverview
Sharks express an unusual heavy-chain isotype called IgNAR, whose variable regions bind antigen as independent soluble domains. To further probe affinity maturation of the IgNAR response, we structurally characterized the germline and somatically matured versions of a type II variable (V) region, both in the presence and absence of its antigen, hen egg-white lysozyme. Despite a disulfide bond linking complementarity determining regions (CDRs) 1 and 3, both germline and somatically matured V regions displayed significant structural changes in these CDRs upon complex formation with antigen. Somatic mutations in the IgNAR V region serve to increase the number of contacts with antigen, as reflected by a tenfold increase in affinity, and one of these mutations appears to stabilize the CDR3 region. In addition, a residue in the HV4 loop plays an important role in antibody-antigen interaction, consistent with the high rate of somatic mutations in this non-CDR loop.
About this StructureAbout this Structure
Full crystallographic information is available from OCA.
ReferenceReference
Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding., Stanfield RL, Dooley H, Verdino P, Flajnik MF, Wilson IA, J Mol Biol. 2007 Mar 23;367(2):358-72. Epub 2006 Dec 22. PMID:17258766 Page seeded by OCA on Sun May 4 06:59:11 2008