Next Article in Journal / Special Issue
The Role of Non-Native Interactions in the Folding of Knotted Proteins: Insights from Molecular Dynamics Simulations
Previous Article in Journal / Special Issue
Toxin Instability and Its Role in Toxin Translocation from the Endoplasmic Reticulum to the Cytosol
Article Menu

Export Article

Open AccessReview
Biomolecules 2013, 3(4), 1030-1052; doi:10.3390/biom3041030

Protein Stability, Folding and Misfolding in Human PGK1 Deficiency

1
Dipartimento di Biologia e Biotecnologie "L. Spallanzani", Università degli Studi di Pavia, Viale Taramelli, 3B, Pavia 27100, Italy
2
Department of Physical Chemistry, Faculty of Science, University of Granada, Av. Fuentenueva s/n, Granada 18071, Spain
*
Author to whom correspondence should be addressed.
Received: 21 October 2013 / Revised: 6 December 2013 / Accepted: 13 December 2013 / Published: 18 December 2013
(This article belongs to the Special Issue Protein Folding and Misfolding)
View Full-Text   |   Download PDF [873 KB, uploaded 18 December 2013]   |  

Abstract

Conformational diseases are often caused by mutations, altering protein folding and stability in vivo. We review here our recent work on the effects of mutations on the human phosphoglycerate kinase 1 (hPGK1), with a particular focus on thermodynamics and kinetics of protein folding and misfolding. Expression analyses and in vitro biophysical studies indicate that disease-causing mutations enhance protein aggregation propensity. We found a strong correlation among protein aggregation propensity, thermodynamic stability, cooperativity and dynamics. Comparison of folding and unfolding properties with previous reports in PGKs from other species suggests that hPGK1 is very sensitive to mutations leading to enhance protein aggregation through changes in protein folding cooperativity and the structure of the relevant denaturation transition state for aggregation. Overall, we provide a mechanistic framework for protein misfolding of hPGK1, which is insightful to develop new therapeutic strategies aimed to target native state stability and foldability in hPGK1 deficient patients. View Full-Text
Keywords: protein misfolding; protein aggregation; conformational disease; pharmacological therapies; molecular chaperones; thermodynamic stability; kinetic stability; proteolysis protein misfolding; protein aggregation; conformational disease; pharmacological therapies; molecular chaperones; thermodynamic stability; kinetic stability; proteolysis
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Valentini, G.; Maggi, M.; Pey, A.L. Protein Stability, Folding and Misfolding in Human PGK1 Deficiency. Biomolecules 2013, 3, 1030-1052.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top