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PDBsum entry 4i3r
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Viral protein/immune system
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PDB id
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4i3r
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Contents |
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190 a.a.
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228 a.a.
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208 a.a.
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PDB id:
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Viral protein/immune system
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Title:
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Crystal structure of the outer domain of HIV-1 gp120 in complex with vrc-pg04 space group p3221
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Structure:
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Outer domain of HIV-1 gp120 (ker2018 od4.2.2). Chain: g. Engineered: yes. Heavy chain of vrc-pg04 fab. Chain: h. Engineered: yes. Light chain of vrc-pg04 fab. Chain: l. Engineered: yes
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Source:
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Human immunodeficiency virus. Organism_taxid: 12721. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: 293s. Homo sapiens. Human. Organism_taxid: 9606. Expression_system_cell_line: 293f.
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Resolution:
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3.00Å
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R-factor:
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0.186
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R-free:
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0.245
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Authors:
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M.G.Joyce,C.Biertumpfel,G.J.Nabel,P.D.Kwong
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Key ref:
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M.G.Joyce
et al.
(2013).
Outer domain of HIV-1 gp120: antigenic optimization, structural malleability, and crystal structure with antibody VRC-PG04.
J Virol,
87,
2294-2306.
PubMed id:
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Date:
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26-Nov-12
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Release date:
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09-Jan-13
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PROCHECK
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Headers
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References
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Q3ZLH8
(Q3ZLH8_9HIV1) -
Envelope glycoprotein gp160 from Human immunodeficiency virus 1
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Seq:
Struc:
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857 a.a.
190 a.a.*
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J Virol
87:2294-2306
(2013)
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PubMed id:
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Outer domain of HIV-1 gp120: antigenic optimization, structural malleability, and crystal structure with antibody VRC-PG04.
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M.G.Joyce,
M.Kanekiyo,
L.Xu,
C.Biertümpfel,
J.C.Boyington,
S.Moquin,
W.Shi,
X.Wu,
Y.Yang,
Z.Y.Yang,
B.Zhang,
A.Zheng,
T.Zhou,
J.Zhu,
J.R.Mascola,
P.D.Kwong,
G.J.Nabel.
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ABSTRACT
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The outer domain of the HIV-1 gp120 envelope glycoprotein contains the epitope
for broadly neutralizing antibodies directed to the CD4-binding site, many of
which are able to neutralize over 90% of circulating HIV-1 isolates. While the
outer domain is conformationally more stable than other portions of the HIV-1
envelope, efforts to express the outer domain as an immunogen for eliciting
broadly neutralizing antibodies have not been successful, potentially because
natural outer domain variants do not bind strongly to antibodies such as VRC01.
In this study, we optimized the antigenic properties of the HIV-1 Env outer
domain to generate OD4.2.2, from the KER2018 strain of clade A HIV-1, enabling
it to bind antibodies such as VRC01 with nanomolar affinity. The crystal
structure of OD4.2.2 in complex with VRC-PG04 was solved at 3.0-Å resolution
and compared to known crystal structures including (i) the structure of core
gp120 bound by VRC-PG04 and (ii) a circularly permutated version of the outer
domain in complex with antibody PGT128. Much of the VRC-PG04 epitope was
preserved in the OD4.2.2 structure, though with altered N and C termini
conformations. Overall, roughly one-third of the outer domain structure appeared
to be fixed in conformation, independent of alterations in termini, clade, or
ligand, while other portions of the outer domain displayed substantial
structural malleability. The crystal structure of OD4.2.2 with VRC-PG04 provides
atomic-level details for an HIV-1 domain recognized by broadly neutralizing
antibodies and insights relevant to the rational design of an immunogen that
could elicit such antibodies by vaccination.
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Links
