3NA4

D53P beta-2 microglobulin mutant


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.217 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

D-strand perturbation and amyloid propensity in beta-2 microglobulin

Azinas, S.Colombo, M.Barbiroli, A.Santambrogio, C.Giorgetti, S.Raimondi, S.Bonomi, F.Grandori, R.Bellotti, V.Ricagno, S.Bolognesi, M.

(2011) FEBS J 278: 2349-2358

  • DOI: https://doi.org/10.1111/j.1742-4658.2011.08157.x
  • Primary Citation of Related Structures:  
    3NA4

  • PubMed Abstract: 

    Proteins hosting main β-sheets adopt specific strategies to avoid intermolecular interactions leading to aggregation and amyloid deposition. Human beta-2 microglobulin (β2m) displays a typical immunoglobulin fold and is known to be amyloidogenic in vivo. Upon severe kidney deficiency, β2m accumulates in the bloodstream, triggering, over the years, pathological deposition of large amyloid aggregates in joints and bones. A β-bulge observed on the edge D β-strand of some β2m crystal structures has been suggested to be crucial in protecting the protein from amyloid aggregation. Conversely, a straight D-strand, observed in different crystal structures of monomeric β2m, could promote amyloid aggregation. More recently, the different conformations observed for the β2m D-strand have been interpreted as the result of intrinsic flexibility, rather than being assigned to a functional protective role against aggregation. To shed light on such contrasting picture, the mutation Asp53→Pro was engineered in β2m, aiming to impair the formation of a regular/straight D-strand. Such a mutant was characterized structurally and biophysically by CD, X-ray crystallography and MS, in addition to an assessment of its amyloid aggregation trends in vitro. The results reported in the present study highlight the conformational plasticity of the edge D-strand, and show that even perturbing the D-strand structure through a Pro residue has only marginal effects on protecting β2m from amyloid aggregation in vitro.


  • Organizational Affiliation

    Dipartimento di Scienze Biomolecolari e Biotecnologie and CIMAINA, Università degli Studi di Milano, Milan, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-2-microglobulin100Homo sapiensMutation(s): 1 
Gene Names: NM_004048
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
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
PE4
Query on PE4

Download Ideal Coordinates CCD File 
B [auth A]2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL
C16 H34 O8
PJWQOENWHPEPKI-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CSO
Query on CSO
A
L-PEPTIDE LINKINGC3 H7 N O3 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.269 
  • R-Value Work: 0.211 
  • R-Value Observed: 0.217 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 29.07α = 90
b = 50.73β = 90
c = 71.18γ = 90
Software Package:
Software NamePurpose
MXdata collection
MOLREPphasing
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-06-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2014-02-19
    Changes: Database references
  • Version 1.3: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2023-11-22
    Changes: Data collection