6UCF

N123-VRC34_pI4 HIV neutralizing antibody in complex with HIV fusion peptide residue 512-519


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.29 Å
  • R-Value Free: 0.182 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.168 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

VRC34-Antibody Lineage Development Reveals How a Required Rare Mutation Shapes the Maturation of a Broad HIV-Neutralizing Lineage.

Shen, C.H.DeKosky, B.J.Guo, Y.Xu, K.Gu, Y.Kilam, D.Ko, S.H.Kong, R.Liu, K.Louder, M.K.Ou, L.Zhang, B.Chao, C.W.Corcoran, M.M.Feng, E.Huang, J.Normandin, E.O'Dell, S.Ransier, A.Rawi, R.Sastry, M.Schmidt, S.D.Wang, S.Wang, Y.Chuang, G.Y.Doria-Rose, N.A.Lin, B.Zhou, T.Boritz, E.A.Connors, M.Douek, D.C.Karlsson Hedestam, G.B.Sheng, Z.Shapiro, L.Mascola, J.R.Kwong, P.D.

(2020) Cell Host Microbe 27: 531

  • DOI: https://doi.org/10.1016/j.chom.2020.01.027
  • Primary Citation of Related Structures:  
    6UBI, 6UCE, 6UCF

  • PubMed Abstract: 

    Rare mutations have been proposed to restrict the development of broadly neutralizing antibodies against HIV-1, but this has not been explicitly demonstrated. We hypothesized that such rare mutations might be identified by comparing broadly neutralizing and non-broadly neutralizing branches of an antibody-developmental tree. Because sequences of antibodies isolated from the fusion peptide (FP)-targeting VRC34-antibody lineage suggested it might be suitable for such rare mutation analysis, we carried out next-generation sequencing (NGS) on B cell transcripts from donor N123, the source of the VRC34 lineage, and functionally and structurally characterized inferred intermediates along broadly neutralizing and poorly neutralizing developmental branches. The broadly neutralizing VRC34.01 branch required the rare heavy-chain mutation Y33P to bind FP, whereas the early bifurcated VRC34.05 branch did not require this rare mutation and evolved less breadth. Our results demonstrate how a required rare mutation can restrict development and shape the maturation of a broad HIV-1-neutralizing antibody lineage.


  • Organizational Affiliation

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
N123-VRC34_pI4 light chainA [auth L]213Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q6GMX0 (Homo sapiens)
Explore Q6GMX0 
Go to UniProtKB:  Q6GMX0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6GMX0
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
N123-VRC34_pI4 heavy chainB [auth H]229Homo 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:  Sequence   |   3D Structure  

Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
HIV fusion peptideC [auth A]8Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for P04578 (Human immunodeficiency virus type 1 group M subtype B (isolate HXB2))
Explore P04578 
Go to UniProtKB:  P04578
Entity Groups  
UniProt GroupP04578
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.29 Å
  • R-Value Free: 0.182 
  • R-Value Work: 0.167 
  • R-Value Observed: 0.168 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 38.42α = 90
b = 86.434β = 90
c = 128.657γ = 90
Software Package:
Software NamePurpose
HKL-2000data scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2020-03-18
    Type: Initial release
  • Version 1.1: 2020-04-22
    Changes: Database references