4NJ9

Crystal structure of Fab 8B10 in complex with MPTS


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 

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Ligand Structure Quality Assessment 


This is version 1.4 of the entry. See complete history


Literature

Adaptive Mutations Alter Antibody Structure and Dynamics during Affinity Maturation.

Adhikary, R.Yu, W.Oda, M.Walker, R.C.Chen, T.Stanfield, R.L.Wilson, I.A.Zimmermann, J.Romesberg, F.E.

(2015) Biochemistry 54: 2085-2093

  • DOI: https://doi.org/10.1021/bi501417q
  • Primary Citation of Related Structures:  
    4NJ9, 4NJA

  • PubMed Abstract: 

    While adaptive mutations can bestow new functions on proteins via the introduction or optimization of reactive centers, or other structural changes, a role for the optimization of protein dynamics also seems likely but has been more difficult to evaluate. Antibody (Ab) affinity maturation is an example of adaptive evolution wherein the adaptive mutations may be identified and Abs may be raised to specific targets that facilitate the characterization of protein dynamics. Here, we report the characterization of three affinity matured Abs that evolved from a common germline precursor to bind the chromophoric antigen (Ag), 8-methoxypyrene-1,3,6-trisulfonate (MPTS). In addition to characterizing the sequence, molecular recognition, and structure of each Ab, we characterized the dynamics of each complex by determining their mechanical response to an applied force via three-pulse photon echo peak shift (3PEPS) spectroscopy and deconvoluting the response into elastic, anelastic, and plastic components. We find that for one Ab, affinity maturation was accomplished via the introduction of a single functional group that mediates a direct contact with MPTS and results in a complex with little anelasticity or plasticity. In the other two cases, more mutations were introduced but none directly contact MPTS, and while their effects on structure are subtle, their effects on anelasticity and plasticity are significant, with the level of plasticity correlated with specificity, suggesting that the optimization of protein dynamics may have contributed to affinity maturation. A similar optimization of structure and dynamics may contribute to the evolution of other proteins.


  • Organizational Affiliation

    §Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, 1-5, Hangi-cho, Shimogamo, Sakyo-ku, Kyoto 606-8522, Japan.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
8B10 light chainA [auth L]218Mus musculusMutation(s): 0 
UniProt
Find proteins for Q52L95 (Mus musculus)
Explore Q52L95 
Go to UniProtKB:  Q52L95
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ52L95
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
8B10 heavy chainB [auth H]229Mus musculusMutation(s): 0 
UniProt
Find proteins for Q9D8L4 (Mus musculus)
Explore Q9D8L4 
Go to UniProtKB:  Q9D8L4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9D8L4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.264 
  • R-Value Work: 0.214 
  • R-Value Observed: 0.217 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 37.133α = 90
b = 58.441β = 90
c = 212.852γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-11-12
    Type: Initial release
  • Version 1.1: 2015-01-21
    Changes: Refinement description
  • Version 1.2: 2015-03-25
    Changes: Database references, Structure summary
  • Version 1.3: 2015-04-08
    Changes: Database references
  • Version 1.4: 2017-06-14
    Changes: Database references, Source and taxonomy