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PDBsum entry 2osl
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Immune system
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PDB id
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2osl
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Contents |
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213 a.a.
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224 a.a.
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20 a.a.
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22 a.a.
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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 basis for recognition of cd20 by therapeutic antibody rituximab.
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Authors
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J.Du,
H.Wang,
C.Zhong,
B.Peng,
M.Zhang,
B.Li,
S.Huo,
Y.Guo,
J.Ding.
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Ref.
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J Biol Chem, 2007,
282,
15073-15080.
[DOI no: ]
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PubMed id
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Abstract
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Rituximab is a widely used monoclonal antibody drug for treating certain
lymphomas and autoimmune diseases. To understand the molecular mechanism of
recognition of human CD20 by Rituximab, we determined the crystal structure of
the Rituximab Fab in complex with a synthesized peptide comprising the CD20
epitope (residues 163-187) at 2.6-A resolution. The combining site of the Fab
consists of four complementarity determining regions that form a large, deep
pocket to accommodate the epitope peptide. The bound peptide assumes a unique
cyclic conformation that is constrained by a disulfide bond and a rigid proline
residue (Pro(172)). The (170)ANPS(173) motif of CD20 is deeply embedded into the
pocket on the antibody surface and plays an essential role in the recognition
and binding of Rituximab. The antigen-antibody interactions involve both
hydrogen bonds and van der Waals contacts and display a high degree of
structural and chemical complementarity. These results provide a molecular basis
for the specific recognition of CD20 by Rituximab as well as valuable
information for development of improved antibody drugs with better specificity
and higher affinity.
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Figure 1.
FIGURE 1. Overall structure of the Rituximab Fab-CD20
epitope-peptide complex. A, overall structure of the complex.
The Rituximab Fab is colored with the light chain in yellow and
the heavy chain in green, and the CD20 epitope peptide in cyan.
B, a stereoview of a composite-omit electron density map at
2.6-Å resolution for the bound epitope peptide contoured
at 1.0-  level. The atomic
coordinates of the peptide residues are shown in ball and stick
models. C, structure of the bound epitope peptide. The epitope
peptide consists of a short N-terminal coil (residues 167-171),
a 3[10] helix (residues 172-174), a small loop (residues
175-177), and a short C-terminal  -helix (residues
178-184). The intra-peptide hydrogen-bonding interactions
between residues of the middle part (the 3[10] helix and the
small loop) and the other parts of the peptide are indicated
with dashed lines.
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Figure 2.
FIGURE 2. Interactions between the Rituximab Fab and the
epitope peptide. A, an overview showing the interactions of the
epitope peptide with the Rituximab Fab. The Fab CDRs are shown
with the H1 loop in orange, H2 in green, H3 in tinted green, L1
in gold, L2 in pink, and L3 in purple. The peptide is colored in
cyan. The four CDR loops (H1, H2, H3, and L3) of the Fab form a
pocket to accommodate the epitope peptide. B, an electrostatic
potential surface of the Rituximab Fab in the region of the
epitope peptide binding pocket showing the structural and
chemical complementarity between the Fab and the bound peptide.
The residues of the epitope peptide involved in interactions
with the Fab are shown with ball and stick models. The
^170ANPS^173 motif of the CD20 epitope is located in a pocket
formed by CDR loops H1, H2, H3, and L3 of the Fab. The locations
of a few residues of the Fab are labeled for reference. C, a
stereoview showing the hydrogen-bonding interactions between
residues of the epitope peptide and CDR loops H1 and H3 of the
Fab. The color coding of the structural elements is the same as
A. D, a stereoview showing the hydrogen bonding between the
epitope peptide and CDR loops H2 and L3 of the Fab.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
15073-15080)
copyright 2007.
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