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PDBsum entry 1rzg
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Immune system
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PDB id
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1rzg
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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 basis of tyrosine sulfation and vh-Gene usage in antibodies that recognize the HIV type 1 coreceptor-Binding site on gp120.
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Authors
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C.C.Huang,
M.Venturi,
S.Majeed,
M.J.Moore,
S.Phogat,
M.Y.Zhang,
D.S.Dimitrov,
W.A.Hendrickson,
J.Robinson,
J.Sodroski,
R.Wyatt,
H.Choe,
M.Farzan,
P.D.Kwong.
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Ref.
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Proc Natl Acad Sci U S A, 2004,
101,
2706-2711.
[DOI no: ]
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PubMed id
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Abstract
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The conserved surface of the HIV-1 gp120 envelope glycoprotein that binds to the
HIV-1 coreceptor is protected from humoral recognition by multiple layers of
camouflage. Here we present sequence and genomic analyses for 12 antibodies that
pierce these defenses and determine the crystal structures of 5. The data reveal
mechanisms and atomic-level details for three unusual immune features:
posttranslational mimicry of coreceptor by tyrosine sulfation of antibody, an
alternative molecular mechanism controlling such sulfation, and highly selective
V(H)-gene usage. When confronted by extraordinary viral defenses, the immune
system unveils novel adaptive capabilities, with tyrosine sulfation enhancing
the vocabulary of antigen recognition.
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Figure 1.
Fig. 1. Structure of the archetype CD4i antibody, 17b. (A)
Complexed versus free structure of 17b. The Left two structures
show the rerefined YU2 and HXBc2 ternary complexes after
superposition of the 17b V[H] framework, with the two complexed
Fab 17b in black C^  worm, interacting 17b
side chains in green, the N-terminal domain of CD4 in yellow,
and the molecular surface of YU2 core gp120 in red, except for
the surface within 3.5 Å of 17b, which is blue. In this
orientation, the viral membrane would be positioned toward the
top of the page. The Right two structures show the two
independent copies of free 17b from the P2[1]2[1]2[1] crystals
superimposed on the complexed structures. The color and
orientation for the complexed structures are the same as in
Left, with the free 17b structures shown in blue with magenta
interactive residues. The Far Right shows the entire Fab,
including the constant portion. Whereas the variable domains are
quite similar, considerable differences are seen in the constant
portions, especially between the two free structures. (B)
Details of gp120-17b interaction at CDR H2 and CDR H3. The
electrostatic potential of gp120 is shown at the molecular
surface colored blue for electropositive, red for acidic, and
white for apolar. The Left two structures show 17b in the same
orientation as A. The portion corresponding to the V[H] gene,
VH1-69, has been colored green, except for residues altered by
somatic mutation, which are colored magenta. The five side
chains of the CDR H2 that interact with gp120 are shown: I52,
I53, L54, V56, and H58. The Right two structures show an  90°
view, adjusted so that the pseudo twofold axes of the Fab are
aligned with the edges of the page. In this view, the acidic CDR
H3 loop (yellow C^ worm) can be seen
reaching up to contact a basic gp120 surface. Side chains of
VH1-69 that interact with the CDR H3 loop are shown.
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Figure 5.
Fig. 5. Atomic-level details of antibody sulfation. The
sulfated tyrosine at position H100 of 412d is shown. Two of the
five coordinating ligands (Lys-145 and Gln-147) are from the
light chain of a symmetry-related molecule. Electron density
(2F[o] - F[c]) is shown at 0.5  .
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