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(+ 0 more)
212 a.a.
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(+ 0 more)
239 a.a.
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* Residue conservation analysis
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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 fab pg16, a broadly reactive and potent HIV-1 neutralizing antibody
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Structure:
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Antibody pg16 light chain. Chain: a, c, e, g, i, k. Engineered: yes. Antibody pg16 heavy chain. Chain: b, d, f, h, j, l. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek 293s gnti -/-. Expression_system_cell_line: hek 293s gnti -/-
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Resolution:
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2.49Å
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R-factor:
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0.209
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R-free:
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0.249
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Authors:
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R.Pejchal,L.M.Walker,D.R.Burton,I.A.Wilson
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Key ref:
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R.Pejchal
et al.
(2010).
Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1.
Proc Natl Acad Sci U S A,
107,
11483-11488.
PubMed id:
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Date:
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03-May-10
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Release date:
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16-Jun-10
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PROCHECK
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Headers
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References
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Proc Natl Acad Sci U S A
107:11483-11488
(2010)
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PubMed id:
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Structure and function of broadly reactive antibody PG16 reveal an H3 subdomain that mediates potent neutralization of HIV-1.
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R.Pejchal,
L.M.Walker,
R.L.Stanfield,
S.K.Phogat,
W.C.Koff,
P.Poignard,
D.R.Burton,
I.A.Wilson.
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ABSTRACT
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Development of an effective vaccine against HIV-1 will likely require
elicitation of broad and potent neutralizing antibodies against the trimeric
surface envelope glycoprotein (Env). Monoclonal antibodies (mAbs) PG9 and PG16
neutralize approximately 80% of HIV-1 isolates across all clades with
extraordinary potency and target novel epitopes preferentially expressed on Env
trimers. As these neutralization properties are ideal for a vaccine-elicited
antibody response to HIV-1, their structural basis was investigated. The crystal
structure of the antigen-binding fragment (Fab) of PG16 at 2.5 A resolution
revealed its unusually long, 28-residue, complementarity determining region
(CDR) H3 forms a unique, stable subdomain that towers above the antibody
surface. A 7-residue "specificity loop" on the "hammerhead" subdomain was
identified that, when transplanted from PG16 to PG9 and vice versa, accounted
for differences in the fine specificity and neutralization of these two mAbs.
The PG16 electron density maps also revealed that a CDR H3 tyrosine was
sulfated, which was confirmed for both PG9 (doubly) and PG16 (singly) by mass
spectral analysis. We further showed that tyrosine sulfation plays a role in
binding and neutralization. An N-linked glycan modification is observed in the
variable light chain, but not required for antigen recognition. Further, the
crystal structure of the PG9 light chain at 3.0 A facilitated homology modeling
to support the presence of these unusual features in PG9. Thus, PG9 and PG16 use
unique structural features to mediate potent neutralization of HIV-1 that may be
of utility in antibody engineering and for high-affinity recognition of a
variety of therapeutic targets.
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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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D.C.Ekiert,
A.K.Kashyap,
J.Steel,
A.Rubrum,
G.Bhabha,
R.Khayat,
J.H.Lee,
M.A.Dillon,
R.E.O'Neil,
A.M.Faynboym,
M.Horowitz,
L.Horowitz,
A.B.Ward,
P.Palese,
R.Webby,
R.A.Lerner,
R.R.Bhatt,
and
I.A.Wilson
(2012).
Cross-neutralization of influenza A viruses mediated by a single antibody loop.
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Nature,
489,
526-532.
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PDB codes:
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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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Links
