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PDBsum entry 4jam
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Immune system
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PDB id
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4jam
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References listed in PDB file
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Key reference
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Title
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Co-Evolution of a broadly neutralizing HIV-1 antibody and founder virus.
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Authors
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H.X.Liao,
R.Lynch,
T.Zhou,
F.Gao,
S.M.Alam,
S.D.Boyd,
A.Z.Fire,
K.M.Roskin,
C.A.Schramm,
Z.Zhang,
J.Zhu,
L.Shapiro,
J.C.Mullikin,
S.Gnanakaran,
P.Hraber,
K.Wiehe,
G.Kelsoe,
G.Yang,
S.M.Xia,
D.C.Montefiori,
R.Parks,
K.E.Lloyd,
R.M.Scearce,
K.A.Soderberg,
M.Cohen,
G.Kamanga,
M.K.Louder,
L.M.Tran,
Y.Chen,
F.Cai,
S.Chen,
S.Moquin,
X.Du,
M.G.Joyce,
S.Srivatsan,
B.Zhang,
A.Zheng,
G.M.Shaw,
B.H.Hahn,
T.B.Kepler,
B.T.Korber,
P.D.Kwong,
J.R.Mascola,
B.F.Haynes,
J.Becker,
B.Benjamin,
R.Blakesley,
G.Bouffard,
S.Brooks,
H.Coleman,
M.Dekhtyar,
M.Gregory,
X.Guan,
J.Gupta,
J.Han,
A.Hargrove,
S.L.Ho,
T.Johnson,
R.Legaspi,
S.Lovett,
Q.Maduro,
C.Masiello,
B.Maskeri,
J.Mcdowell,
C.Montemayor,
J.Mullikin,
M.Park,
N.Riebow,
K.Schandler,
B.Schmidt,
C.Sison,
M.Stantripop,
J.Thomas,
P.Thomas,
M.Vemulapalli,
A.Young.
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Ref.
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Nature, 2013,
496,
469-476.
[DOI no: ]
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PubMed id
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Abstract
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Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific
neutralizing antibodies. However, cross-reactive neutralizing antibodies arise
in approximately 20% of HIV-1-infected individuals, and details of their
generation could provide a blueprint for effective vaccination. Here we report
the isolation, evolution and structure of a broadly neutralizing antibody from
an African donor followed from the time of infection. The mature antibody,
CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal
structure with the HIV-1 envelope protein gp120 revealed a new loop-based
mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing
revealed concomitant virus evolution and antibody maturation. Notably, the
unmutated common ancestor of the CH103 lineage avidly bound the
transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody
neutralization breadth was preceded by extensive viral diversification in and
near the CH103 epitope. These data determine the viral and antibody evolution
leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and
provide insights into strategies to elicit similar antibodies by vaccination.
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