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PDBsum entry 2i25
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Immune system
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PDB id
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2i25
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References listed in PDB file
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Key reference
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Title
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Maturation of shark single-Domain (ignar) antibodies: evidence for induced-Fit binding.
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Authors
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R.L.Stanfield,
H.Dooley,
P.Verdino,
M.F.Flajnik,
I.A.Wilson.
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Ref.
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J Mol Biol, 2007,
367,
358-372.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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.
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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.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(2007,
367,
358-372)
copyright 2007.
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