4NWT

Crystal structure of the anti-human NGF Fab APE1531


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.150 
  • R-Value Observed: 0.152 

Starting Models: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Nucleotide insertions and deletions complement point mutations to massively expand the diversity created by somatic hypermutation of antibodies.

Bowers, P.M.Verdino, P.Wang, Z.da Silva Correia, J.Chhoa, M.Macondray, G.Do, M.Neben, T.Y.Horlick, R.A.Stanfield, R.L.Wilson, I.A.King, D.J.

(2014) J Biol Chem 289: 33557-33567

  • DOI: https://doi.org/10.1074/jbc.M114.607176
  • Primary Citation of Related Structures:  
    4NWT, 4NWU

  • PubMed Abstract: 

    During somatic hypermutation (SHM), deamination of cytidine by activation-induced cytidine deaminase and subsequent DNA repair generates mutations within immunoglobulin V-regions. Nucleotide insertions and deletions (indels) have recently been shown to be critical for the evolution of antibody binding. Affinity maturation of 53 antibodies using in vitro SHM in a non-B cell context was compared with mutation patterns observed for SHM in vivo. The origin and frequency of indels seen during in vitro maturation were similar to that in vivo. Indels are localized to CDRs, and secondary mutations within insertions further optimize antigen binding. Structural determination of an antibody matured in vitro and comparison with human-derived antibodies containing insertions reveal conserved patterns of antibody maturation. These findings indicate that activation-induced cytidine deaminase acting on V-region sequences is sufficient to initiate authentic formation of indels in vitro and in vivo and that point mutations, indel formation, and clonal selection form a robust tripartite system for antibody evolution.


  • Organizational Affiliation

    From Anaptysbio Inc., San Diego, California 92121 and pbowers@anaptysbio.com.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
APE1531 Ab Fab light chainA [auth L]220Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q8TCD0 (Homo sapiens)
Explore Q8TCD0 
Go to UniProtKB:  Q8TCD0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ8TCD0
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
APE1531 Ab Fab heavy chainB [auth H]233Homo sapiensMutation(s): 0 
Gene Names: IGHG1
UniProt & NIH Common Fund Data Resources
Find proteins for P01857 (Homo sapiens)
Explore P01857 
Go to UniProtKB:  P01857
PHAROS:  P01857
GTEx:  ENSG00000211896 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01857
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.75 Å
  • R-Value Free: 0.181 
  • R-Value Work: 0.150 
  • R-Value Observed: 0.152 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 127.72α = 90
b = 64.36β = 108.67
c = 63.81γ = 90
Software Package:
Software NamePurpose
Web-Icedata collection
PHASERphasing
REFMACrefinement
XDSdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-10-22
    Type: Initial release
  • Version 1.1: 2014-10-29
    Changes: Database references
  • Version 1.2: 2014-12-10
    Changes: Database references
  • Version 1.3: 2017-08-02
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2021-06-02
    Changes: Database references, Derived calculations, Refinement description, Source and taxonomy
  • Version 1.5: 2023-09-20
    Changes: Data collection, Database references, Refinement description