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PDBsum entry 4khx
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Immune system
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PDB id
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4khx
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Contents |
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66 a.a.
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208 a.a.
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205 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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Crystal structure of gp41 helix complexed with antibody 8062
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Structure:
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Gp41 helix. Chain: a. Engineered: yes. 8062 heavy chain. Chain: h. 8062 light chain. Chain: l
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Source:
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Human immunodeficiency virus 1. Organism_taxid: 11676. Expressed in: escherichia coli. Expression_system_taxid: 562. Homo sapiens. Organism_taxid: 9606. Organism_taxid: 9606
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Resolution:
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2.92Å
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R-factor:
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0.239
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R-free:
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0.290
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Authors:
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M.Li,A.Gustchina,A.Wlodawer
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Key ref:
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E.Gustchina
et al.
(2013).
Complexes of neutralizing and non-neutralizing affinity matured Fabs with a mimetic of the internal trimeric coiled-coil of HIV-1 gp41.
Plos One,
8,
e78187.
PubMed id:
DOI:
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Date:
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01-May-13
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Release date:
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12-Mar-14
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PROCHECK
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Headers
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References
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A1YNW7
(A1YNW7_9HIV1) -
Env polyprotein (Fragment) from Human immunodeficiency virus 1
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Seq:
Struc:
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74 a.a.
66 a.a.*
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DOI no:
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Plos One
8:e78187
(2013)
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PubMed id:
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Complexes of neutralizing and non-neutralizing affinity matured Fabs with a mimetic of the internal trimeric coiled-coil of HIV-1 gp41.
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E.Gustchina,
M.Li,
R.Ghirlando,
P.Schuck,
J.M.Louis,
J.Pierson,
P.Rao,
S.Subramaniam,
A.Gustchina,
G.M.Clore,
A.Wlodawer.
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ABSTRACT
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A series of mini-antibodies (monovalent and bivalent Fabs) targeting the
conserved internal trimeric coiled-coil of the N-heptad repeat (N-HR) of HIV-1
gp41 has been previously constructed and reported. Crystal structures of two
closely related monovalent Fabs, one (Fab 8066) broadly neutralizing across a
wide panel of HIV-1 subtype B and C viruses, and the other (Fab 8062)
non-neutralizing, representing the extremes of this series, were previously
solved as complexes with 5-Helix, a gp41 pre-hairpin intermediate mimetic.
Binding of these Fabs to covalently stabilized chimeric trimers of N-peptides of
HIV-1 gp41 (named (CCIZN36)3 or 3-H) has now been investigated using X-ray
crystallography, cryo-electron microscopy, and a variety of biophysical methods.
Crystal structures of the complexes between 3-H and Fab 8066 and Fab 8062 were
determined at 2.8 and 3.0 Å resolution, respectively. Although the structures
of the complexes with the neutralizing Fab 8066 and its non-neutralizing
counterpart Fab 8062 were generally similar, small differences between them
could be correlated with the biological properties of these antibodies. The
conformations of the corresponding CDRs of each antibody in the complexes with
3-H and 5-Helix are very similar. The adaptation to a different target upon
complex formation is predominantly achieved by changes in the structure of the
trimer of N-HR helices, as well as by adjustment of the orientation of the Fab
molecule relative to the N-HR in the complex, via rigid-body movement. The
structural data presented here indicate that binding of three Fabs 8062 with
high affinity requires more significant changes in the structure of the N-HR
trimer compared to binding of Fab 8066. A comparative analysis of the structures
of Fabs complexed to different gp41 intermediate mimetics allows further
evaluation of biological relevance for generation of neutralizing antibodies, as
well as provides novel structural insights into immunogen design.
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Links
