Conformational stability and folding mechanisms of dimeric proteins.
Decreased stability and increased formation of soluble aggregates by immature superoxide dismutase do not account for disease severity in ALS
- Kenrick A. Vassall, Helen R Stubbs, E. Meiering
- BiologyProceedings of the National Academy of Sciences
- 21 January 2011
In contrast with previous studies, it is found that various reduced apo SOD1 mutants undergo highly reversible thermal denaturation with little aggregation, enabling quantitative thermodynamic stability analyses and suggesting that reduced api S OD1 does not play a dominant role in modulating disease.
MyelStones: the executive roles of myelin basic protein in myelin assembly and destabilization in multiple sclerosis.
Progress is discussed in the understanding of conformational conversions of this classic basic protein upon membrane association, including new thermodynamic analyses of transitions into different structural ensembles and how a shift in the pattern of its post-translational modifications is associated with the pathogenesis and potentially onset of demyelination in MS.
The Effects of Threonine Phosphorylation on the Stability and Dynamics of the Central Molecular Switch Region of 18.5-kDa Myelin Basic Protein
- Kenrick A. Vassall, K. Bessonov, Miguel De Avila, E. Polverini, G. Harauz
- Biology, ChemistryPLoS ONE
- 5 July 2013
The results support the hypothesis that the central conserved segment of MBP constitutes a molecular switch in which the conformation and/or intermolecular interactions are mediated by phosphorylation/dephosphorylation at T92 and T95.
Equilibrium thermodynamic analysis of amyotrophic lateral sclerosis-associated mutant apo Cu,Zn superoxide dismutases.
- Kenrick A. Vassall, P. Stathopulos, J. Rumfeldt, J. Lepock, E. Meiering
- Chemistry, BiologyBiochemistry
- 18 May 2006
Analysis of DSC data for apo SODs is consistent with stability measurements from GdmCl curves and provides further evidence for increased aggregation by mutant proteins through increased ratios of van't Hoff to calorimetric enthalpies of unfolding.
Destabilization of the dimer interface is a common consequence of diverse ALS‐associated mutations in metal free SOD1
- Helen R. Broom, J. Rumfeldt, Kenrick A. Vassall, E. Meiering
- Biology, ChemistryProtein Science
- 1 December 2015
Direct measurement of the thermodynamic effects of chemically and structurally diverse mutations on the stability of the dimer interface for metal free (apo) SOD1 using isothermal titration calorimetry and size exclusion chromatography indicates substantial structural perturbations accompany dimer dissociation, resulting in the formation of poorly packed and malleable dissociated monomers.
The proline-rich region of 18.5 kDa myelin basic protein binds to the SH3-domain of Fyn tyrosine kinase with the aid of an upstream segment to form a dynamic complex in vitro
- Miguel De Avila, Kenrick A. Vassall, Graham S. T. Smith, V. Bamm, G. Harauz
- Biology, ChemistryBioscience Reports
- 24 October 2014
This work shows that an MBP segment upstream of the primary ligand is involved in MBP–Fyn–SH3 association in cellula, and defines this segment to comprise MBP residues (T62–L68), and demonstrates further that residues (V83–P93) are the predominant SH3-target, assessed by the degree of chemical shift change upon titration.
Energetics of oligomeric protein folding and association.
Substitutions mimicking deimination and phosphorylation of 18.5-kDa myelin basic protein exert local structural effects that subtly influence its global folding.
The Classic Basic Protein of Myelin–Conserved Structural Motifs and the Dynamic Molecular Barcode Involved in Membrane Adhesion, Protein-Protein Interactions, and Pathogenesis in Multiple Sclerosis