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PDBsum entry 2eh8
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Immune system
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PDB id
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2eh8
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References listed in PDB file
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Key reference
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Title
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Broadly neutralizing anti-Hepatitis b virus antibody reveals a complementarity determining region h3 lid-Opening mechanism.
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Authors
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S.W.Chi,
C.Y.Maeng,
S.J.Kim,
M.S.Oh,
C.J.Ryu,
S.J.Kim,
K.H.Han,
H.J.Hong,
S.E.Ryu.
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Ref.
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Proc Natl Acad Sci U S A, 2007,
104,
9230-9235.
[DOI no: ]
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PubMed id
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Abstract
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The humanized monoclonal antibody HzKR127 recognizes the preS1 domain of the
human hepatitis B virus surface proteins with a broadly neutralizing activity in
vivo. We present the crystal structures of HzKR127 Fab and its complex with a
major epitope peptide. In the complex structure, the bound peptide forms a type
IV beta-turn followed by 3(10) helical turn, the looped-out conformation of
which provides a structural basis for broad neutralization. Upon peptide
binding, the antibody undergoes a dramatic complementarity determining region H3
lid opening. To understand the structural implication of the virus
neutralization, we carried out comprehensive alanine-scanning mutagenesis of all
complementarity determining region residues in HzKR127 Fab. The functional
mapping of the antigen-combining site demonstrates the specific roles of major
binding determinants in antigen binding, contributing to the rational design for
maximal humanization and affinity maturation of the antibody.
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Figure 1.
Fig. 1. Domains of HBV surface proteins. The domain
structures of S, M, and L proteins are presented with each
domain colored differently. The adr subtype preS1 includes an
epitope that is recognized by the neutralizing monoclonal
antibody HzKR127. The peptide sequence of the epitope region is
presented below the preS1 domain, with the epitope colored red.
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Figure 3.
Fig. 3. Comparison of antigen-binding site in the free and
bound HzKR127 Fabs. Interactions between the H3 lid (yellow) and
neighbors in the free (Left) and bound (Right) HzKR127 Fabs. The
residues involved in the interactions are drawn, and the major
interactions are presented as dotted lines. The light and heavy
chains are colored pink and blue (labeled red and blue),
respectively. The bound peptide residues Pro6P–Trp8P are
presented as sticks with atomic colors.
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