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* Residue conservation analysis
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Structure
1:83-93
(1993)
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PubMed id:
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Major antigen-induced domain rearrangements in an antibody.
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R.L.Stanfield,
M.Takimoto-Kamimura,
J.M.Rini,
A.T.Profy,
I.A.Wilson.
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ABSTRACT
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BACKGROUND: Recent structural results have shown that antibodies use an induced
fit mechanism to recognize and bind their antigens. Here we present the
crystallographically determined structure of an Fab directed against an HIV-1
peptide (Fab 50.1) in the unliganded state and compare it with the peptide-bound
structure. We perform a detailed analysis of the components that contribute to
enhanced antigen binding and recognition. RESULTS: Induced fit of Fab 50.1 to
its peptide antigen involves a substantial rearrangement of the third
complementarity determining region loop of the heavy chain (H3), as well as a
large rotation of the variable heavy (VH) chain relative to the variable light
(VL) chain. Analysis of other Fab structures suggests that the extent of the
surface area buried at the VL-VH interface correlates with the ability to alter
antibody quaternary structure by reorientation of the VL-VH domains. CONCLUSION:
Fab 50.1 exhibits the largest conformational changes yet observed in a single
antibody. These can be attributed to the flexibility of the variable region.
Comparisons of new data with previous examples lend to the general conclusion
that a small VL-VH interface, due in part to a short H3 loop, permits
substantial alterations to the antigen-binding pocket. This has major
implications for the prediction, engineering and design of antibody-combining
sites.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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PDB code:
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PDB codes:
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PDB codes:
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J Biol Chem,
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PDB codes:
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A.P.Campbell,
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Proc Natl Acad Sci U S A,
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PDB code:
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C.A.Sotriffer,
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Biophys J,
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Structure,
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PDB code:
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PDB codes:
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J.J.Boniface,
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J Biol Chem,
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PDB codes:
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Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs.
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Structure,
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PDB codes:
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S.Kumar,
B.Ma,
C.J.Tsai,
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Cell Biochem Biophys,
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Antiidiotypic antibody recognizes an amiloride binding domain within the alpha subunit of the epithelial Na+ channel.
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J Biol Chem,
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Atomic structure of an alphabeta T cell receptor (TCR) heterodimer in complex with an anti-TCR fab fragment derived from a mitogenic antibody.
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EMBO J,
17,
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PDB code:
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K.C.Garcia,
M.Degano,
L.R.Pease,
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P.A.Peterson,
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and
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(1998).
Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen.
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Science,
279,
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PDB code:
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K.M.Arndt,
K.M.Müller,
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A.Plückthun
(1998).
Factors influencing the dimer to monomer transition of an antibody single-chain Fv fragment.
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Biochemistry,
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Imperfect interfaces.
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One of the CD3epsilon subunits within a T cell receptor complex lies in close proximity to the Cbeta FG loop.
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X-ray structures of a hydrolytic antibody and of complexes elucidate catalytic pathway from substrate binding and transition state stabilization through water attack and product release.
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Proc Natl Acad Sci U S A,
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PDB codes:
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C.H.Trinh,
S.D.Hemmington,
M.E.Verhoeyen,
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Antibody fragment Fv4155 bound to two closely related steroid hormones: the structural basis of fine specificity.
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Structure,
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PDB codes:
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D.B.Smithrud,
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Biochemistry,
36,
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PDB code:
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L.W.Guddat,
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The uncharged surface features surrounding the active site of Escherichia coli DsbA are conserved and are implicated in peptide binding.
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VL:VH domain rotations in engineered antibodies: crystal structures of the Fab fragments from two murine antitumor antibodies and their engineered human constructs.
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PDB codes:
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T.Keitel,
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Crystallographic analysis of anti-p24 (HIV-1) monoclonal antibody cross-reactivity and polyspecificity.
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PDB codes:
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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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PDB code:
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A.Desmyter,
T.R.Transue,
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PDB code:
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PDB codes:
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D.R.Davies,
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I.M.Tomlinson,
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A.M.Lesk,
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Conformational similarity and systematic displacement of complementarity determining region loops in high resolution antibody x-ray structures.
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J Biol Chem,
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R.Crainic,
and
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(1995).
Structure of the complex between the Fab fragment of a neutralizing antibody for type 1 poliovirus and its viral epitope.
|
| |
Nat Struct Biol,
2,
232-243.
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|
PDB code:
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|
R.L.Stanfield,
and
I.A.Wilson
(1995).
Protein-peptide interactions.
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| |
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B.Golinelli-Pimpaneau,
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D.S.Tawfik,
Z.Eshhar,
B.S.Green,
and
M.Knossow
(1994).
Crystal structure of a catalytic antibody Fab with esterase-like activity.
|
| |
Structure,
2,
175-183.
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|
PDB code:
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|
C.A.Janeway
(1994).
Thymic selection: two pathways to life and two to death.
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Immunity,
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In vitro evolution of a neutralizing human antibody to human immunodeficiency virus type 1 to enhance affinity and broaden strain cross-reactivity.
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Proc Natl Acad Sci U S A,
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I.A.Wilson,
and
R.L.Stanfield
(1994).
Antibody-antigen interactions: new structures and new conformational changes.
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| |
Curr Opin Struct Biol,
4,
857-867.
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J.Tormo,
D.Blaas,
N.R.Parry,
D.Rowlands,
D.Stuart,
and
I.Fita
(1994).
Crystal structure of a human rhinovirus neutralizing antibody complexed with a peptide derived from viral capsid protein VP2.
|
| |
EMBO J,
13,
2247-2256.
|
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|
PDB code:
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P.M.Colman
(1994).
Influenza virus neuraminidase: structure, antibodies, and inhibitors.
|
| |
Protein Sci,
3,
1687-1696.
|
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R.L.Stanfield,
and
I.A.Wilson
(1994).
Antigen-induced conformational changes in antibodies: a problem for structural prediction and design.
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| |
Trends Biotechnol,
12,
275-279.
|
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|
The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
code is
shown on the right.
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