5CKA

Human beta-2 microglobulin double mutant W60G-N83V


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.70 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.181 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability.

Camilloni, C.Sala, B.M.Sormanni, P.Porcari, R.Corazza, A.De Rosa, M.Zanini, S.Barbiroli, A.Esposito, G.Bolognesi, M.Bellotti, V.Vendruscolo, M.Ricagno, S.

(2016) Sci Rep 6: 25559-25559

  • DOI: https://doi.org/10.1038/srep25559
  • Primary Citation of Related Structures:  
    5CFH, 5CKA, 5CKG

  • PubMed Abstract: 

    A wide range of human diseases is associated with mutations that, destabilizing proteins native state, promote their aggregation. However, the mechanisms leading from folded to aggregated states are still incompletely understood. To investigate these mechanisms, we used a combination of NMR spectroscopy and molecular dynamics simulations to compare the native state dynamics of Beta-2 microglobulin (β2m), whose aggregation is associated with dialysis-related amyloidosis, and its aggregation-resistant mutant W60G. Our results indicate that W60G low aggregation propensity can be explained, beyond its higher stability, by an increased average protection of the aggregation-prone residues at its surface. To validate these findings, we designed β2m variants that alter the aggregation-prone exposed surface of wild-type and W60G β2m modifying their aggregation propensity. These results allowed us to pinpoint the role of dynamics in β2m aggregation and to provide a new strategy to tune protein aggregation by modulating the exposure of aggregation-prone residues.


  • Organizational Affiliation

    Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin100Homo sapiensMutation(s): 2 
Gene Names: B2MCDABP0092HDCMA22P
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: 1.70 Å
  • R-Value Free: 0.226 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.181 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.98α = 90
b = 28.91β = 128.57
c = 57.32γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Italian Ministry of University and ResearchItalyFIRB RBFR109EOS

Revision History  (Full details and data files)

  • Version 1.0: 2016-05-18
    Type: Initial release
  • Version 1.1: 2024-01-10
    Changes: Data collection, Database references, Refinement description