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PDBsum entry 3g3b
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Hydrolase/immune system
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PDB id
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3g3b
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Contents |
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169 a.a.
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127 a.a.
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159 a.a.
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71 a.a.
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References listed in PDB file
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Key reference
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Title
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Structure of a lamprey variable lymphocyte receptor in complex with a protein antigen.
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Authors
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C.A.Velikovsky,
L.Deng,
S.Tasumi,
L.M.Iyer,
M.C.Kerzic,
L.Aravind,
Z.Pancer,
R.A.Mariuzza.
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Ref.
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Nat Struct Biol, 2009,
16,
725-730.
[DOI no: ]
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PubMed id
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Abstract
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Variable lymphocyte receptors (VLRs) are leucine-rich repeat proteins that
mediate adaptive immunity in jawless vertebrates. VLRs are fundamentally
different from the antibodies of jawed vertebrates, which consist of
immunoglobulin (Ig) domains. We determined the structure of an anti-hen egg
white lysozyme (HEL) VLR, isolated by yeast display, bound to HEL. The VLR,
whose affinity resembles that of IgM antibodies, uses nearly all its concave
surface to bind the protein, in addition to a loop that penetrates into the
enzyme active site. The VLR-HEL structure combined with sequence analysis
revealed an almost perfect match between ligand-contacting positions and
positions with highest sequence diversity. Thus, it is likely that we have
defined the generalized antigen-binding site of VLRs. We further demonstrated
that VLRs can be affinity-matured by 13-fold to affinities as high as those of
IgG antibodies, making VLRs potential alternatives to antibodies for
biotechnology applications.
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Figure 1.
(a) Ribbon diagram of the VLRB.2D–HEL complex showing the
concave antigen-binding surface of the VLR solenoid. LRRNT,
yellow; LRR1, LRRV1 and LRRVe, blue; CP, red; LRRCT, orange;
HEL, green; residue numbers corresponding to each module in
parentheses. (b) The complex is oriented to highlight the
interaction between the LRRCT insert and the active site cleft
of HEL.
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Figure 3.
Residues involved in contacts are depicted as surface
representation. (a) Binding surface of VLRB.2D with contacting
residues from LRR1, LRRV and LRRVe in blue, from CP in red and
from LRRCT in orange. (b) Binding surface of VLR RBC36 (cyan) in
the complex with H-saccharide based on the structure PDB 3E6J^4.
(c,d) Comparison of VLR and antibody epitopes on HEL. Binding
surfaces of HEL in the VLRB.2D–HEL complex (c) and camel
cAb-Lys3–HEL based on the complex structure PDB 1MEL^14 (d).
Residues forming contacts in both complexes are green; residues
that interact exclusively with VLRB.2D or cAb-Ly3 are violet.
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The above figures are
reprinted
from an Open Access publication published by Macmillan Publishers Ltd:
Nat Struct Biol
(2009,
16,
725-730)
copyright 2009.
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