2I25

Crystal structure analysis of the nurse shark New antigen Receptor PBLA8 variable domain in complex with lysozyme

Summary for 2I25

• Entry DOI: 10.2210/pdb2i25/pdb
• Related: 2I24 2I26 2I27
• Descriptor: New Antigen Receptor PBLA8, Lysozyme C (3 entities in total)
• Functional Keywords: immunoglobulin fold, protein-protein complex, immune system
• Biological source: Ginglymostoma cirratum (nurse shark); More
• Cellular location: Secreted: P00698
• Total number of polymer chains: 4
• Total formula weight: 55537.93

Authors

Stanfield, R.L.,Wilson, I.A. (deposition date: 2006-08-15, release date: 2007-03-06, Last modification date: 2024-10-30)

Primary citation

Stanfield, R.L.,Dooley, H.,Verdino, P.,Flajnik, M.F.,Wilson, I.A.
Maturation of Shark Single-domain (IgNAR) Antibodies: Evidence for Induced-fit Binding
J.Mol.Biol., 367:358-372, 2007

PubMed Abstract: 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.

PubMed: 17258766
DOI: 10.1016/j.jmb.2006.12.045

Experimental method

X-RAY DIFFRACTION (1.8 Å)