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(+ 0 more)
224 a.a.
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209 a.a.
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PDB id:
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Immune system
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Title:
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Crystal structure of human 2909 fab, a quaternary structure-specific antibody against HIV-1
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Structure:
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Human monoclonal antibody 2909 fab heavy chain. Chain: h, a, c, e, g, j. Engineered: yes. Human monoclonal antibody 2909 fab light chain. Chain: l, b, d, f, i, k. Engineered: yes
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Source:
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Homo sapiens. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293f.
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Resolution:
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3.33Å
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R-factor:
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0.240
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R-free:
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0.299
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Authors:
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A.Changela,M.K.Gorny,S.Zolla-Pazner,P.D.Kwong
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Key ref:
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A.Changela
et al.
(2011).
Crystal structure of human antibody 2909 reveals conserved features of quaternary structure-specific antibodies that potently neutralize HIV-1.
J Virol,
85,
2524-2535.
PubMed id:
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Date:
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07-Nov-10
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Release date:
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05-Jan-11
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PROCHECK
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Headers
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References
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J Virol
85:2524-2535
(2011)
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PubMed id:
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Crystal structure of human antibody 2909 reveals conserved features of quaternary structure-specific antibodies that potently neutralize HIV-1.
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A.Changela,
X.Wu,
Y.Yang,
B.Zhang,
J.Zhu,
G.A.Nardone,
S.O'Dell,
M.Pancera,
M.K.Gorny,
S.Phogat,
J.E.Robinson,
L.Stamatatos,
S.Zolla-Pazner,
J.R.Mascola,
P.D.Kwong.
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ABSTRACT
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Monoclonal antibody 2909 belongs to a class of potently neutralizing antibodies
that recognize quaternary epitopes on HIV-1. Some members of this class, such as
2909, are strain specific, while others, such as antibody PG16, are broadly
neutralizing; all, however, recognize a region on the gp120 envelope
glycoprotein that includes two loops (V2 and V3) and forms appropriately only in
the oligomeric HIV-1 spike (gp120(3)/gp41(3)). Here we present the crystal
structure of 2909 and report structure-function analysis with antibody chimeras
composed of 2909 and other members of this antibody class. The 2909 structure
was dominated by a heavy-chain third-complementarity-determining region (CDR H3)
of 21 residues, which comprised 36% of the combining surface and formed a
β-hairpin club extending ∼20 Å beyond the rest of the antibody. Sequence
analysis and mass spectrometry identified sites of tyrosine sulfation at the
middle and top of CDR H3; substitutions with phenylalanine either ablated
(middle substitution) or substantially diminished (top substitution)
neutralization. Chimeric antibodies composed of heavy and light chains,
exchanged between 2909 and other members of the class, indicated a substantial
lack of complementation. Comparison of 2909 to PG16 (which is tyrosine sulfated
and the only other member of the class for which a structure has previously been
reported) showed that both utilize protruding, anionic CDR H3s for recognition.
Thus, despite some diversity, members of this class share structural and
functional similarities, with conserved features of the CDR H3 subdomain likely
reflecting prevalent solutions by the human immune system for recognition of a
quaternary site of HIV-1 vulnerability.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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J.S.McLellan,
M.Pancera,
C.Carrico,
J.Gorman,
J.P.Julien,
R.Khayat,
R.Louder,
R.Pejchal,
M.Sastry,
K.Dai,
S.O'Dell,
N.Patel,
S.Shahzad-ul-Hussan,
Y.Yang,
B.Zhang,
T.Zhou,
J.Zhu,
J.C.Boyington,
G.Y.Chuang,
D.Diwanji,
I.Georgiev,
Y.D.Kwon,
D.Lee,
M.K.Louder,
S.Moquin,
S.D.Schmidt,
Z.Y.Yang,
M.Bonsignori,
J.A.Crump,
S.H.Kapiga,
N.E.Sam,
B.F.Haynes,
D.R.Burton,
W.C.Koff,
L.M.Walker,
S.Phogat,
R.Wyatt,
J.Orwenyo,
L.X.Wang,
J.Arthos,
C.A.Bewley,
J.R.Mascola,
G.J.Nabel,
W.R.Schief,
A.B.Ward,
I.A.Wilson,
and
P.D.Kwong
(2011).
Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9.
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Nature,
480,
336-343.
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PDB codes:
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The most recent references are shown first.
Citation data come partly from CiteXplore and partly
from an automated harvesting procedure. Note that this is likely to be
only a partial list as not all journals are covered by
either method. However, we are continually building up the citation data
so more and more references will be included with time.
Where a reference describes a PDB structure, the PDB
codes are
shown on the right.
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