2XKS

Prion-like conversion during amyloid formation at atomic resolution


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 30 
  • Conformers Submitted: 30 
  • Selection Criteria: LOWEST ENERGY 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Conformational Conversion During Amyloid Formation at Atomic Resolution.

Eichner, T.Kalverda, A.P.Thompson, G.S.Homans, S.W.Radford, S.E.

(2011) Mol Cell 41: 161-172

  • DOI: https://doi.org/10.1016/j.molcel.2010.11.028
  • Primary Citation of Related Structures:  
    2XKS, 2XKU

  • PubMed Abstract: 

    Numerous studies of amyloid assembly have indicated that partially folded protein species are responsible for initiating aggregation. Despite their importance, the structural and dynamic features of amyloidogenic intermediates and the molecular details of how they cause aggregation remain elusive. Here, we use ΔN6, a truncation variant of the naturally amyloidogenic protein β(2)-microglobulin (β(2)m), to determine the solution structure of a nonnative amyloidogenic intermediate at high resolution. The structure of ΔN6 reveals a major repacking of the hydrophobic core to accommodate the nonnative peptidyl-prolyl trans-isomer at Pro32. These structural changes, together with a concomitant pH-dependent enhancement in backbone dynamics on a microsecond-millisecond timescale, give rise to a rare conformer with increased amyloidogenic potential. We further reveal that catalytic amounts of ΔN6 are competent to convert nonamyloidogenic human wild-type β(2)m (Hβ(2)m) into a rare amyloidogenic conformation and provide structural evidence for the mechanism by which this conformational conversion occurs.


  • Organizational Affiliation

    Astbury Centre for Structural Molecular Biology and Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
BETA-2-MICROGLOBULIN99Homo 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: SOLUTION NMR
  • Conformers Calculated: 30 
  • Conformers Submitted: 30 
  • Selection Criteria: LOWEST ENERGY 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-02-16
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-01-17
    Changes: Data collection, Database references
  • Version 1.4: 2020-01-15
    Changes: Data collection, Other