2X89

Structure of the Beta2_microglobulin involved in amyloidogenesis


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.240 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Atomic Structure of a Nanobody-Trapped Domain-Swapped Dimer of an Amyloidogenic {Beta}2-Microglobulin Variant.

Domanska, K.Vanderhaegen, S.Srinivasan, V.Pardon, E.Dupeux, F.Marquez, J.A.Giorgetti, S.Stoppini, M.Wyns, L.Bellotti, V.Steyaert, J.

(2011) Proc Natl Acad Sci U S A 108: 1314

  • DOI: https://doi.org/10.1073/pnas.1008560108
  • Primary Citation of Related Structures:  
    2X89

  • PubMed Abstract: 

    Atomic-level structural investigation of the key conformational intermediates of amyloidogenesis remains a challenge. Here we demonstrate the utility of nanobodies to trap and characterize intermediates of β2-microglobulin (β2m) amyloidogenesis by X-ray crystallography. For this purpose, we selected five single domain antibodies that block the fibrillogenesis of a proteolytic amyloidogenic fragment of β2m (ΔN6β2m). The crystal structure of ΔN6β2m in complex with one of these nanobodies (Nb24) identifies domain swapping as a plausible mechanism of self-association of this amyloidogenic protein. In the swapped dimer, two extended hinge loops--corresponding to the heptapetide NHVTLSQ that forms amyloid in isolation--are unmasked and fold into a new two-stranded antiparallel β-sheet. The β-strands of this sheet are prone to self-associate and stack perpendicular to the direction of the strands to build large intermolecular β-sheets that run parallel to the axis of growing oligomers, providing an elongation mechanism by self-templated growth.


  • Organizational Affiliation

    Department of Molecular and Cellular Interactions, Vlaams Instituut voor Biotechnologie, Pleinlaan 2, B-1050 Brussels, Belgium.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
ANTIBODY
A, B, C
128Camelus dromedariusMutation(s): 0 
UniProt
Find proteins for A2KD59 (Lama glama)
Explore A2KD59 
Go to UniProtKB:  A2KD59
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA2KD59
Sequence Annotations
Expand
  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-2-MICROGLOBULIN
D, E, F, G
94Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P61769 (Homo sapiens)
Explore P61769 
Go to UniProtKB:  P61769
PHAROS:  P61769
GTEx:  ENSG00000166710 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP61769
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.16 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.238 
  • R-Value Observed: 0.240 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.49α = 90
b = 100.864β = 106.43
c = 83.743γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKLdata reduction
SCALEPACKdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-01-19
    Type: Initial release
  • Version 1.1: 2013-09-04
    Changes: Derived calculations, Other, Refinement description, Source and taxonomy, Version format compliance
  • Version 1.2: 2023-12-20
    Changes: Data collection, Database references, Other, Refinement description