2AGJ

Crystal Structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


This is version 3.1 of the entry. See complete history


Literature

Crystal structure of a glycosylated Fab from an IgM cryoglobulin with properties of a natural proteolytic antibody

Ramsland, P.A.Terzyan, S.S.Cloud, G.Bourne, C.R.Farrugia, W.Tribbick, G.Geysen, H.M.Moomaw, C.R.Slaughter, C.A.Edmundson, A.B.

(2006) Biochem J 395: 473-481

  • DOI: https://doi.org/10.1042/BJ20051739
  • Primary Citation of Related Structures:  
    2AGJ

  • PubMed Abstract: 

    The 2.6 A (1 A=0.1 nm) resolution structure has been determined for the glycosylated Fab (fragment antigen binding) of an IgM (Yvo) obtained from a subject with Waldenström's macroglobulinaemia. Dynamic light scattering was used to estimate the gel point and monitor the formation of an ordered hydroscopic gel of Yvo IgM upon cooling. If a cryoglobulin forms gels in peripheral tissues and organs, the associated swelling and damage to microvasculature can result in considerable morbidity and mortality. The three-dimensional structure of the branched N-linked oligosaccharide associated with the CH1 domain (first constant domain of heavy chain) is reported. The carbohydrate may act to shield part of the lateral surface of the CH1 domain and crowd the junction between the CH1 and CH2 domains, thereby limiting the segmental flexibility of the Fab arms in intact Yvo IgM, especially at low temperatures. Recently, Yvo IgM was shown to have the properties of a naturally occurring proteolytic antibody [Paul, Karle, Planque, Taguchi, Salas, Nishiyama, Handy, Hunter, Edmundson and Hanson (2004) J. Biol. Chem. 279, 39611-39619; Planque, Bangale, Song, Karle, Taguchi, Poindexter, Bick, Edmundson, Nishiyama and Paul (2004) J. Biol Chem. 279, 14024-14032]. The Yvo protein displayed the ability to cleave, by a nucleophilic mechanism, the amide bonds of a variety of serine protease substrates and the gp120 coat protein of HIV. An atypical serine, arginine and glutamate motif is located in the middle of the Yvo antigen-binding site and displays an overall geometry that mimics the classical serine, histidine and aspartate catalytic triad of serine proteases. Our present findings indicate that pre-existing or natural antibodies can utilize at least one novel strategy for the cleavage of peptide bonds.


  • Organizational Affiliation

    Structural Immunology Laboratory, Austin Research Institute, Kronheimer Building, Austin Health, Studley Road, Heidelberg, VIC 3084, Australia. p.ramsland@ari.unimelb.edu.au


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Yvo Fab, Light ChainA [auth L]215Homo sapiensMutation(s): 0 
UniProt
Find proteins for Q6PJF2 (Homo sapiens)
Explore Q6PJF2 
Go to UniProtKB:  Q6PJF2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6PJF2
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Yvo Fab, Heavy ChainB [auth H]226Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P01871 (Homo sapiens)
Explore P01871 
Go to UniProtKB:  P01871
PHAROS:  P01871
GTEx:  ENSG00000211899 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP01871
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranoseC [auth A]2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PCA
Query on PCA
B [auth H]L-PEPTIDE LINKINGC5 H7 N O3GLN
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.279 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.225 
  • Space Group: I 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.433α = 90
b = 103.653β = 90
c = 138.715γ = 90
Software Package:
Software NamePurpose
MAR345data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-05-02
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2017-10-11
    Changes: Refinement description
  • Version 2.0: 2019-12-25
    Changes: Derived calculations, Polymer sequence
  • Version 3.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 3.1: 2023-10-25
    Changes: Data collection, Database references, Refinement description, Structure summary