PDBsum entry 1ves

Immune system

PDB id: 1ves

Contents

Protein chains

113 a.a. *

Waters ×358

* Residue conservation analysis

PDB id:

1ves

Name:

Immune system

Title:

Structure of new antigen receptor variable domain from sharks

Structure:

New antigen receptor variable domain. Chain: a, b. Synonym: vnar. Engineered: yes

Source:

Orectolobus maculatus. Spotted wobbegong. Organism_taxid: 168098. Expressed in: escherichia coli. Expression_system_taxid: 562.

Biol. unit:

Dimer (from PQS)

Resolution:

2.18Å R-factor: 0.179 R-free: 0.247

Authors:

V.A.Streltsov

Key ref:

V.A.Streltsov et al. (2004). Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor. Proc Natl Acad Sci U S A, 101, 12444-12449. PubMed id: 15304650 DOI: 10.1073/pnas.0403509101

Date:

05-Apr-04 Release date: 24-Aug-04

Protein chains

Q6X1E6  (Q6X1E6_9CHON) -  New antigen receptor variable domain (Fragment) from Orectolobus maculatus

Seq: 113 a.a.

Struc: 113 a.a.

DOI no: 10.1073/pnas.0403509101

Proc Natl Acad Sci U S A 101:12444-12449 (2004)

PubMed id: 15304650

Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor.

V.A.Streltsov, J.N.Varghese, J.A.Carmichael, R.A.Irving, P.J.Hudson, S.D.Nuttall.

ABSTRACT

The Ig new antigen receptors (IgNARs) are single-domain antibodies found in the serum of sharks. Here, we report 2.2- and 2.8-A structures of the type 2 IgNAR variable domains 12Y-1 and 12Y-2. Structural features include, first, an Ig superfamily topology transitional between cell adhesion molecules, antibodies, and T cell receptors; and, second, a vestigial complementarity-determining region 2 at the "bottom" of the molecule, apparently discontinuous from the antigen-binding paratope and similar to that observed in cell adhesion molecules. Thus, we suggest that IgNARs originated as cell-surface adhesion molecules coopted to the immune repertoire and represent an evolutionary lineage independent of variable heavy chain/variable light chain type antibodies. Additionally, both 12Y-1 and 12Y-2 form unique crystallographic dimers, predominantly mediated by main-chain framework interactions, which represent a possible model for primordial cell-based interactions. Unusually, the 12Y-2 complementarity-determining region 3 also adopts an extended beta-hairpin structure, suggesting a distinct selective advantage in accessing cryptic antigenic epitopes.

Selected figure(s)

Figure 2.
Fig. 2. VMD (44) stereo images of superimposed IgSF domains in ribbon representation. (a) The 12Y-2 A chain (red), 12Y-2 B chain (blue), and 12Y-1 (yellow). (b) The 12Y-2 A chain (red), telokin (blue) [Protein Data Bank (PDB) ID code 1FHG [PDB] ], and NCAM domain 1 (yellow) (PDB ID code 1QZ1 [PDB] ). (c) The 12Y-2 A chain (red), human TCR V[ ](blue) (PDB ID code 1A07 [PDB] ), human V[H] (green) and V[L] (yellow) (PDB ID code 1IGM [PDB] ), and camel V[H]H (cyan) (PDB ID code 1MEL [PDB] ).

Figure 3.
Fig. 3. VMD (44) molecular surfaces for variable domains. (a) V[NAR] 12Y-2 chain A. (b) Camel V[H]H (PDB ID code 1MEL [PDB] ). (c) Human TCR V[ ](PDB ID code 1A07 [PDB] ). (d) Human V[H] (PDB ID code 1IGM [PDB] ). (e) NCAM domain 1 (PDB ID code1QZ1). (f) Telokin (PDB ID code 1FHG [PDB] ). A closeup view of the V[H]/V[L] type interface is shown for each molecule (boxed area), with some residues visible in licorice-like representation through the transparent surface. Blue, red, and green correspond to basic, acidic, and polar residues, respectively. Dashed lines are H bonds ( 3.0 Å).

Figures were selected by an automated process.