PDBsum entry 2i27

Immune system

PDB id: 2i27

Contents

Protein chains

109 a.a. *

Waters ×81

* Residue conservation analysis

PDB id:

2i27

Name:

Immune system

Title:

Crystal structure analysis of the nurse shark new antigen receptor ancestral variable domain

Structure:

New antigen receptor ancestral. Chain: n, o. Fragment: variable domain. Engineered: yes

Source:

Ginglymostoma cirratum. Nurse shark. Organism_taxid: 7801. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.92Å R-factor: 0.220 R-free: 0.281

Authors:

R.L.Stanfield,I.A.Wilson

Key ref:

R.L.Stanfield et al. (2007). Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding. J Mol Biol, 367, 358-372. PubMed id: 17258766 DOI: 10.1016/j.jmb.2006.12.045

Date:

15-Aug-06 Release date: 06-Mar-07

Protein chains

Q8JGJ1  (Q8JGJ1_GINCI) -  Antigen receptor (Fragment) from Ginglymostoma cirratum

Seq: 119 a.a.

Struc: 109 a.a.*

* PDB and UniProt seqs differ at 10 residue positions (black crosses)

DOI no: 10.1016/j.jmb.2006.12.045

J Mol Biol 367:358-372 (2007)

PubMed id: 17258766

Maturation of shark single-domain (IgNAR) antibodies: evidence for induced-fit binding.

R.L.Stanfield, H.Dooley, P.Verdino, M.F.Flajnik, I.A.Wilson.

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.

Selected figure(s)

Figure 3.
Figure 3. Different CDR1–CDR3 contacts in Ancestral and PBLA8. (a) unliganded Ancestral, (b) unliganded PBLA8, (c) liganded Ancestral, (d) liganded PBLA8. Residue 28 is an Asn in the Ancestral structure (a) and an Arg in PBLA8 (b). PBLA8 Arg28 forms a salt-bridge with Asp93 that may serve to stabilize CDR3; this interaction is absent in the Ancestral structure. The PBLA8 Arg28-Asp93 salt-bridge must be broken to bind lysozyme (d) where Asp93 forms a salt-bridge with lysozyme residue ArgL112. Figure 3. Different CDR1–CDR3 contacts in Ancestral and PBLA8. (a) unliganded Ancestral, (b) unliganded PBLA8, (c) liganded Ancestral, (d) liganded PBLA8. Residue 28 is an Asn in the Ancestral structure (a) and an Arg in PBLA8 (b). PBLA8 Arg28 forms a salt-bridge with Asp93 that may serve to stabilize CDR3; this interaction is absent in the Ancestral structure. The PBLA8 Arg28-Asp93 salt-bridge must be broken to bind lysozyme (d) where Asp93 forms a salt-bridge with lysozyme residue ArgL112.

Figure 7.
Figure 7. Comparison of IgNAR V domain and human NEW Vλ domain. The NEW Vλ domain has an unusual deletion of the CDR2 region, similar to that seen in the IgNAR V domains. Figure 7. Comparison of IgNAR V domain and human NEW Vλ domain. The NEW Vλ domain has an unusual deletion of the CDR2 region, similar to that seen in the IgNAR V domains.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2007, 367, 358-372) copyright 2007.

Figures were selected by an automated process.