5F9W

Crystal structure of broadly neutralizing VH1-46 germline-derived CD4-binding site-directed antibody CH235 in complex with HIV-1 clade A/E 93TH057 gp120


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.89 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.8 of the entry. See complete history


Literature

Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody.

Bonsignori, M.Zhou, T.Sheng, Z.Chen, L.Gao, F.Joyce, M.G.Ozorowski, G.Chuang, G.Y.Schramm, C.A.Wiehe, K.Alam, S.M.Bradley, T.Gladden, M.A.Hwang, K.K.Iyengar, S.Kumar, A.Lu, X.Luo, K.Mangiapani, M.C.Parks, R.J.Song, H.Acharya, P.Bailer, R.T.Cao, A.Druz, A.Georgiev, I.S.Kwon, Y.D.Louder, M.K.Zhang, B.Zheng, A.Hill, B.J.Kong, R.Soto, C.Mullikin, J.C.Douek, D.C.Montefiori, D.C.Moody, M.A.Shaw, G.M.Hahn, B.H.Kelsoe, G.Hraber, P.T.Korber, B.T.Boyd, S.D.Fire, A.Z.Kepler, T.B.Shapiro, L.Ward, A.B.Mascola, J.R.Liao, H.X.Kwong, P.D.Haynes, B.F.

(2016) Cell 165: 449-463

  • DOI: https://doi.org/10.1016/j.cell.2016.02.022
  • Primary Citation of Related Structures:  
    5F96, 5F9O, 5F9W

  • PubMed Abstract: 

    Antibodies with ontogenies from VH1-2 or VH1-46-germline genes dominate the broadly neutralizing response against the CD4-binding site (CD4bs) on HIV-1. Here, we define with longitudinal sampling from time-of-infection the development of a VH1-46-derived antibody lineage that matured to neutralize 90% of HIV-1 isolates. Structures of lineage antibodies CH235 (week 41 from time-of-infection, 18% breadth), CH235.9 (week 152, 77%), and CH235.12 (week 323, 90%) demonstrated the maturing epitope to focus on the conformationally invariant portion of the CD4bs. Similarities between CH235 lineage and five unrelated CD4bs lineages in epitope focusing, length-of-time to develop breadth, and extraordinary level of somatic hypermutation suggested commonalities in maturation among all CD4bs antibodies. Fortunately, the required CH235-lineage hypermutation appeared substantially guided by the intrinsic mutability of the VH1-46 gene, which closely resembled VH1-2. We integrated our CH235-lineage findings with a second broadly neutralizing lineage and HIV-1 co-evolution to suggest a vaccination strategy for inducing both lineages.


  • Organizational Affiliation

    Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
clade A/E 93TH057 HIV-1 gp120 coreA,
D [auth G]
353Human immunodeficiency virus 1Mutation(s): 0 
Gene Names: HIV-1 Env
UniProt
Find proteins for A0A0M3KKW9 (Human immunodeficiency virus 1)
Explore A0A0M3KKW9 
Go to UniProtKB:  A0A0M3KKW9
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0M3KKW9
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Heavy chain of CH235-lineage antibody CH235B,
E [auth H]
225Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Light chain of CH235-lineage antibody CH235C,
F [auth L]
213Homo sapiensMutation(s): 0 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
NAG
Query on NAG

Download Ideal Coordinates CCD File 
AA [auth G]
BA [auth G]
CA [auth G]
DA [auth G]
EA [auth G]
AA [auth G],
BA [auth G],
CA [auth G],
DA [auth G],
EA [auth G],
FA [auth G],
G [auth A],
GA [auth G],
H [auth A],
HA [auth G],
I [auth A],
IA [auth G],
J [auth A],
K [auth A],
L [auth A],
M [auth A],
N [auth A],
O [auth A],
P [auth A],
Q [auth A],
R [auth A],
S [auth A],
T [auth A],
W [auth G],
X [auth G],
Y [auth G],
Z [auth G]
2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
JA [auth H],
U [auth A],
V [auth B]
PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.89 Å
  • R-Value Free: 0.232 
  • R-Value Work: 0.180 
  • R-Value Observed: 0.182 
  • Space Group: P 32
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 123.429α = 90
b = 123.429β = 90
c = 127.332γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesP01-AI104722
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesUM1 AI100645
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)United StatesUM1 AI100663

Revision History  (Full details and data files)

  • Version 1.0: 2016-03-09
    Type: Initial release
  • Version 1.1: 2016-03-23
    Changes: Database references
  • Version 1.2: 2016-04-20
    Changes: Database references
  • Version 1.3: 2017-09-06
    Changes: Author supporting evidence, Derived calculations
  • Version 1.4: 2017-11-22
    Changes: Database references
  • Version 1.5: 2019-11-06
    Changes: Author supporting evidence, Data collection
  • Version 1.6: 2019-12-11
    Changes: Author supporting evidence
  • Version 1.7: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 1.8: 2023-09-27
    Changes: Data collection, Database references, Refinement description, Structure summary