6MTT

Crystal structure of VRC46.01 Fab in complex with gp41 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.235 
  • R-Value Observed: 0.236 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Longitudinal Analysis Reveals Early Development of Three MPER-Directed Neutralizing Antibody Lineages from an HIV-1-Infected Individual.

Krebs, S.J.Kwon, Y.D.Schramm, C.A.Law, W.H.Donofrio, G.Zhou, K.H.Gift, S.Dussupt, V.Georgiev, I.S.Schatzle, S.McDaniel, J.R.Lai, Y.T.Sastry, M.Zhang, B.Jarosinski, M.C.Ransier, A.Chenine, A.L.Asokan, M.Bailer, R.T.Bose, M.Cagigi, A.Cale, E.M.Chuang, G.Y.Darko, S.Driscoll, J.I.Druz, A.Gorman, J.Laboune, F.Louder, M.K.McKee, K.Mendez, L.Moody, M.A.O'Sullivan, A.M.Owen, C.Peng, D.Rawi, R.Sanders-Buell, E.Shen, C.H.Shiakolas, A.R.Stephens, T.Tsybovsky, Y.Tucker, C.Verardi, R.Wang, K.Zhou, J.Zhou, T.Georgiou, G.Alam, S.M.Haynes, B.F.Rolland, M.Matyas, G.R.Polonis, V.R.McDermott, A.B.Douek, D.C.Shapiro, L.Tovanabutra, S.Michael, N.L.Mascola, J.R.Robb, M.L.Kwong, P.D.Doria-Rose, N.A.

(2019) Immunity 50: 677-691.e13

  • DOI: https://doi.org/10.1016/j.immuni.2019.02.008
  • Primary Citation of Related Structures:  
    6MTO, 6MTP, 6MTQ, 6MTR, 6MTS, 6MTT

  • PubMed Abstract: 

    Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.


  • Organizational Affiliation

    U.S. Military HIV Research Program, WRAIR, Silver Spring, MD, USA; Henry Jackson Foundation, Bethesda, MD, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Antibody VRC46.01 Fb light chainA [auth L]214Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Antibody VRC46.01 Fab heavy chainB [auth H]224Homo sapiensMutation(s): 0 
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
RV217 founder virus gp41 peptideC [auth P]28Human immunodeficiency virus 1Mutation(s): 0 
UniProt
Find proteins for A7L302 (Human immunodeficiency virus 1)
Explore A7L302 
Go to UniProtKB:  A7L302
Entity Groups  
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UniProt GroupA7L302
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.265 
  • R-Value Work: 0.235 
  • R-Value Observed: 0.236 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.602α = 90
b = 49.162β = 97.1
c = 99.967γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Department of Energy (DOE, United States)United StatesW-31-109-Eng-38

Revision History  (Full details and data files)

  • Version 1.0: 2019-03-27
    Type: Initial release
  • Version 1.1: 2019-12-04
    Changes: Author supporting evidence