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PDBsum entry 1ves
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Immune system
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PDB id
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1ves
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Structural evidence for evolution of shark ig new antigen receptor variable domain antibodies from a cell-Surface receptor.
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Authors
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V.A.Streltsov,
J.N.Varghese,
J.A.Carmichael,
R.A.Irving,
P.J.Hudson,
S.D.Nuttall.
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Ref.
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Proc Natl Acad Sci U S A, 2004,
101,
12444-12449.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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]
).
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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).
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