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PDBsum entry 4ydk
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Immune system
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PDB id
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4ydk
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Contents |
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341 a.a.
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230 a.a.
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214 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 repertoire of HIV-1-Neutralizing antibodies targeting the cd4 supersite in 14 donors.
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Authors
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T.Zhou,
R.M.Lynch,
L.Chen,
P.Acharya,
X.Wu,
N.A.Doria-Rose,
M.G.Joyce,
D.Lingwood,
C.Soto,
R.T.Bailer,
M.J.Ernandes,
R.Kong,
N.S.Longo,
M.K.Louder,
K.Mckee,
S.O'Dell,
S.D.Schmidt,
L.Tran,
Z.Yang,
A.Druz,
T.S.Luongo,
S.Moquin,
S.Srivatsan,
Y.Yang,
B.Zhang,
A.Zheng,
M.Pancera,
T.Kirys,
I.S.Georgiev,
T.Gindin,
H.P.Peng,
A.S.Yang,
J.C.Mullikin,
M.D.Gray,
L.Stamatatos,
D.R.Burton,
W.C.Koff,
M.S.Cohen,
B.F.Haynes,
J.P.Casazza,
M.Connors,
D.Corti,
A.Lanzavecchia,
Q.J.Sattentau,
R.A.Weiss,
A.P.West,
P.J.Bjorkman,
J.F.Scheid,
M.C.Nussenzweig,
L.Shapiro,
J.R.Mascola,
P.D.Kwong.
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Ref.
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Cell, 2015,
161,
1280-1292.
[DOI no: ]
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PubMed id
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Abstract
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The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is
recognized by broadly reactive antibodies, several of which neutralize over 90%
of HIV-1 strains. To understand how antibodies achieve such neutralization, we
isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal
structures -8 determined here- of CD4bs antibodies from 14 donors. The 16
antibodies segregated by recognition mode and developmental ontogeny into two
types: CDR H3-dominated and VH-gene-restricted. Both could achieve greater than
80% neutralization breadth, and both could develop in the same donor. Although
paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed
geometric similarity, with antibody-neutralization breadth correlating with
antibody-angle of approach relative to the most effective antibody of each type.
The repertoire for effective recognition of the CD4 supersite thus comprises
antibodies with distinct paratopes arrayed about two optimal geometric
orientations, one achieved by CDR H3 ontogenies and the other achieved by
VH-gene-restricted ontogenies.
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