5EWI

Crystal Structure of the Human Fab VRC38.01, an HIV-1 V1V2-Directed Neutralizing Antibody Isolated from Donor N90


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.174 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Virus-like Particles Identify an HIV V1V2 Apex-Binding Neutralizing Antibody that Lacks a Protruding Loop.

Cale, E.M.Gorman, J.Radakovich, N.A.Crooks, E.T.Osawa, K.Tong, T.Li, J.Nagarajan, R.Ozorowski, G.Ambrozak, D.R.Asokan, M.Bailer, R.T.Bennici, A.K.Chen, X.Doria-Rose, N.A.Druz, A.Feng, Y.Joyce, M.G.Louder, M.K.O'Dell, S.Oliver, C.Pancera, M.Connors, M.Hope, T.J.Kepler, T.B.Wyatt, R.T.Ward, A.B.Georgiev, I.S.Kwong, P.D.Mascola, J.R.Binley, J.M.

(2017) Immunity 46: 777-791.e10

  • DOI: https://doi.org/10.1016/j.immuni.2017.04.011
  • Primary Citation of Related Structures:  
    5EWI, 5VGJ

  • PubMed Abstract: 

    Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, by using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain-to-side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, thereby facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus identifies a solution for V1V2-apex binding that provides a more conventional B cell pathway for vaccine design.


  • 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
VRC38.01 Heavy ChainA [auth H]236Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q6N089 (Homo sapiens)
Explore Q6N089 
Go to UniProtKB:  Q6N089
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6N089
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
VRC38.01 Light ChainB [auth L]220Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01834 (Homo sapiens)
Explore P01834 
Go to UniProtKB:  P01834
PHAROS:  P01834
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01834
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.60 Å
  • R-Value Free: 0.202 
  • R-Value Work: 0.173 
  • R-Value Observed: 0.174 
  • Space Group: P 21 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 62.353α = 90
b = 84.775β = 90
c = 90.003γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
HKL-2000data scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-11-23
    Type: Initial release
  • Version 1.1: 2017-05-24
    Changes: Database references
  • Version 1.2: 2017-05-31
    Changes: Database references
  • Version 1.3: 2023-09-27
    Changes: Data collection, Database references, Refinement description