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PDBsum entry 1q1j
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Immune system
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PDB id
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1q1j
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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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Structural rationale for the broad neutralization of HIV-1 by human monoclonal antibody 447-52d.
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Authors
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R.L.Stanfield,
M.K.Gorny,
C.Williams,
S.Zolla-Pazner,
I.A.Wilson.
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Ref.
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Structure, 2004,
12,
193-204.
[DOI no: ]
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PubMed id
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Abstract
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447-52D is a human monoclonal antibody isolated from a heterohybridoma derived
from an HIV-1-infected individual. This antibody recognizes the hypervariable
gp120 V3 loop, and neutralizes both X4 and R5 primary isolates, making it one of
the most effective anti-V3 antibodies characterized to date. The crystal
structure of the 447-52D Fab in complex with a 16-mer V3 peptide at 2.5 A
resolution reveals that the peptide beta hairpin forms a three-stranded mixed
beta sheet with complementarity determining region (CDR) H3, with most of the V3
side chains exposed to solvent. Sequence specificity is conferred through
interaction of the type-II turn (residues GPGR) at the apex of the V3 hairpin
with the base of CDR H3. This novel mode of peptide-antibody recognition enables
the antibody to bind to many different V3 sequences where only the GPxR core
epitope is absolutely required.
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Figure 6.
Figure 6. Stereo view of the Fab 447-52D Antigen Binding
Site(A) As in all figures except Figure 1, the Fab light and
heavy chains are depicted in salmon and blue, with the bound
peptide in yellow. The side chains of the Fab residues in
contact with peptide are shown in a ball-and-stick
representation.(B) A magnified view of the cation-p and salt
bridge interactions between peptide and Fab. The V3 peptide
residue ArgP315 forms a salt bridge with AspH95, and makes
cation-p interactions with the side chains of TyrH100j and
TrpH33. Peptide residue ProP313 is nestled into a cleft formed
by Fab residues TrpL91 and TrpL96, with the Pro ring nearly
coplanar to the TrpL91 indole.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
193-204)
copyright 2004.
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