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PDBsum entry 1nqb
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Immunoglobulin
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PDB id
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1nqb
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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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The 2.0-A resolution crystal structure of a trimeric antibody fragment with noncognate vh-Vl domain pairs shows a rearrangement of vh cdr3.
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Authors
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X.Y.Pei,
P.Holliger,
A.G.Murzin,
R.L.Williams.
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Ref.
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Proc Natl Acad Sci U S A, 1997,
94,
9637-9642.
[DOI no: ]
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PubMed id
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Note In the PDB file this reference is
annotated as "TO BE PUBLISHED".
The citation details given above were identified by an automated
search of PubMed on title and author
names, giving a
percentage match of
0%.
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Abstract
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The 2.0-A resolution x-ray crystal structure of a novel trimeric antibody
fragment, a "triabody," has been determined. The trimer is made up of
polypeptides constructed in a manner identical to that previously described for
some "diabodies": a VL domain directly fused to the C terminus of a VH
domain-i.e., without any linker sequence. The trimer has three Fv heads with the
polypeptides arranged in a cyclic, head-to-tail fashion. For the particular
structure reported here, the polypeptide was constructed with a VH domain from
one antibody fused to the VL domain from an unrelated antibody giving rise to
"combinatorial" Fvs upon formation of the trimer. The structure shows
that the exchange of the VL domain from antibody B1-8, a Vlambda domain, with
the VL domain from antibody NQ11, a Vkappa domain, leads to a dramatic
conformational change in the VH CDR3 loop of antibody B1-8. The magnitude of
this change is similar to the largest of the conformational changes observed in
antibody fragments in response to antigen binding. Combinatorial pairing of VH
and VL domains constitutes a major component of antibody diversity.
Conformationally flexible antigen-binding sites capable of adapting to the
specific CDR3 loop context created upon VH-VL pairing may be employed by the
immune system to maximize the structural diversity of the immune response.
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Figure 4.
Fig. 4. A comparison of the V[L]-V[H] orientations of the
B1-8 (dashed lines) and B1-8/NQ11 (solid lines) Fvs. The C^  values
of the B1-8 V[H] framework were superimposed on the B1-8/NQ11^
V[H] framework. The C^ positions
of residues GlyH103 and TyrH106 are indicated by spheres (white
for B1-8 and black for B1-8/NQ11).
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Figure 5.
Fig. 5. Stereoview comparisons of the H3 loops in B1-8 and
B1-8/NQ11. (a) A worm representation of the H3 loop in B1-8
(shaded lighter) superimposed on the H3 loop of B1-8/NQ11
(shaded darker). The^ molecular surface shown is that of the
B1-8/NQ11 model with the^ H3 loop omitted. The surface of the
V[H] domain is white and the^ general surface of the V[L] domain
is light gray. The surface of^ Phe^L60 is shaded dark. The
analogous residue in B1-8 is Ala^L57 that leaves space to
accommodate the side chain of TyrH106 (shown in stick
representation) in the B1-8 Fv. The presence^ of GlyL96 (shaded)
leaves space to accommodate the side chain of TyrH106 in
B1-8/NQ11. The analogous volume in B1-8 is occupied by TrpL93.
(b) The H3 loop of B1-8/NQ11 and its interaction with V[  ]residues.
The C^ positions
are indicated with larger spheres. V[L] atoms are shown as white
spheres and V[H] atoms as black spheres. (c) The B1-8 H3^ loop
and its interactions with the V[  ]domain.
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