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PDBsum entry 2qad
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Viral protein/immune system
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PDB id
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2qad
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Contents |
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319 a.a.
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178 a.a.
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213 a.a.
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231 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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Structures of the ccr5 n terminus and of a tyrosine-Sulfated antibody with HIV-1 gp120 and cd4.
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Authors
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C.C.Huang,
S.N.Lam,
P.Acharya,
M.Tang,
S.H.Xiang,
S.S.Hussan,
R.L.Stanfield,
J.Robinson,
J.Sodroski,
I.A.Wilson,
R.Wyatt,
C.A.Bewley,
P.D.Kwong.
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Ref.
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Science, 2007,
317,
1930-1934.
[DOI no: ]
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PubMed id
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Abstract
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The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and
facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are
many antibodies that react with the co-receptor binding site on gp120. We
applied nuclear magnetic resonance and crystallographic techniques to analyze
the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody
412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated
regions of CCR5 (alpha-helix) and 412d (extended loop) are surprisingly
different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces
similar structural rearrangements in gp120. These results now provide a
framework for understanding HIV-1 interactions with the CCR5 N terminus during
viral entry and define a conserved site on gp120, whose recognition of
sulfotyrosine engenders posttranslational mimicry by the immune system.
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Figure 2.
Fig. 2. Structure of the tyrosine-sulfated antibody 412d in
complex with HIV-1 gp120 and CD4. (A) Ribbon representation. CD4
is yellow, the heavy chain of Fab 412d is dark blue, the light
chain is cyan, and gp120 is gray, except for the V3 loop, which
is orange. The CDR H3 loop of 412d is red, with sulfotyrosines
depicted in stick representation. (B) Close-up, with molecular
surface of gp120 in gray and sulfotyrosines of 412d (red labels)
and select residues of gp120 (black labels) in stick
representation. Dotted lines represent coordinating hydrogen
bonds between gp120 and the sulfate group of Tys100c^412d. The
sulfate of Tys 100c^412d makes a full complement of ionic
interactions: a salt bridge to Arg 298^gp120 and hydrogen bonds
to the side-chain nitrogen of Asn 302^gp120, the side-chain
hydroxyl of Thr 303^gp120, and the main-chain amides of
302^gp120, 303^gp120, and 441^gp120 (34).
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Figure 4.
Fig. 4. A conserved site for binding sulfotyrosine on HIV-1
gp120. (A) Alterations of the V3 base to accommodate binding of
sulfotyrosine. The gp120 (gray) region around the V3 loop
(orange) is illustrated in ribbon diagram, with an overlying
semitransparent surface for unbound (left panel) and bound
(right panel) conformations. Binding of the CCR5 N terminus
(purple) or the 412d CDR H3 (red), each with two sulfotyrosines
(stick representation, with red and purple labels), alters the
V3 base, forming a sulfotyrosine binding pocket and a rigid
ß-hairpin. (B) Close-up of the conserved sulfotyrosine
binding pocket. The orientation shown is similar to that in
Figs. 2B and 3B [  90° from (A)
about a diagonal axis, as defined by the long axis of the V3
from (A)]. Tys 14^CCR5 is shown in purple, with Tys 100c^412d in
red. Select residues of gp120 are shown in stick representation
and labeled in black. Hydrogen bonds coordinating the buried
sulfate groups in each are depicted with dotted lines.
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The above figures are
reprinted
by permission from the AAAs:
Science
(2007,
317,
1930-1934)
copyright 2007.
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