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PDBsum entry 1om3
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Immune system
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PDB id
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1om3
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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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Antibody domain exchange is an immunological solution to carbohydrate cluster recognition.
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Authors
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D.A.Calarese,
C.N.Scanlan,
M.B.Zwick,
S.Deechongkit,
Y.Mimura,
R.Kunert,
P.Zhu,
M.R.Wormald,
R.L.Stanfield,
K.H.Roux,
J.W.Kelly,
P.M.Rudd,
R.A.Dwek,
H.Katinger,
D.R.Burton,
I.A.Wilson.
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Ref.
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Science, 2003,
300,
2065-2071.
[DOI no: ]
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PubMed id
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Abstract
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Human antibody 2G12 neutralizes a broad range of human immunodeficiency virus
type 1 (HIV-1) isolates by binding an unusually dense cluster of carbohydrate
moieties on the "silent" face of the gp120 envelope glycoprotein.
Crystal structures of Fab 2G12 and its complexes with the disaccharide
Manalpha1-2Man and with the oligosaccharide Man9GlcNAc2 revealed that two Fabs
assemble into an interlocked VH domain-swapped dimer. Further biochemical,
biophysical, and mutagenesis data strongly support a Fab-dimerized antibody as
the prevalent form that recognizes gp120. The extraordinary configuration of
this antibody provides an extended surface, with newly described binding sites,
for multivalent interaction with a conserved cluster of oligomannose type sugars
on the surface of gp120. The unique interdigitation of Fab domains within an
antibody uncovers a previously unappreciated mechanism for high-affinity
recognition of carbohydrate or other repeating epitopes on cell or microbial
surfaces.
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Figure 4.
Fig. 4. The antibody-combining site interactions with the
disaccharide Man  1-2Man. (A) The
2F[obs] - F[calc] electron density for Man 1-2Man is
contoured at 1.7  and the CDR loops
are labeled. (B) The combining site showing Fab atoms within
hydrogen bonding distance (dotted lines) of Man 1-2Man. The Fab
heavy chain and light chain are shown in purple and cyan,
respectively. We generated the figures using programs Bobscript
(64), Molscript (65), and Raster3D (66).
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Figure 6.
Fig. 6. Model of 2G12 glycan recognition of gp120. On the basis
of our model, three separate Man[9]GlcNAc[2] moieties, shown in
red (two in the primary combining sites and one in the
V[H]/V[H]' interface), potentially mediate the binding of 2G12
to gp120. The glycans at the primary combining sites originate
from Asn332 and Asn392 (labeled) in gp120, whereas the
carbohydrate located at the V[H]/V[H]' interface would arise
from Asn339 (labeled). N-linked glycans occurring at Asn332 and
Asn392 have previously been implicated as critical for 2G12
binding (13). The N-linked glycan at Asn 339 is not as critical
for 2G12 binding, although this glycan could potentially
interact with the V[H]/V[H]' interface. Figure was generated
using programs Molscript (65) and Raster3D (66).
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The above figures are
reprinted
by permission from the AAAs:
Science
(2003,
300,
2065-2071)
copyright 2003.
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