‘Something in the way she moves’: The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI)

Robert B. Freedman, Jasmine L. Desmond, Lee J. Byrne, Jack W. Heal, Mark J. Howard, Narinder Sanghera, Kelly L. Walker, A. Katrine Wallis, Stephen A. Wells, Richard A. Williamson, Rudolf A. Römer

Research output: Contribution to journalReview article

10 Citations (Scopus)

Abstract

Protein disulfide isomerase (PDI) has diverse functions in the endoplasmic reticulum as catalyst of redox transfer, disulfide isomerization and oxidative protein folding, as molecular chaperone and in multi-subunit complexes. It interacts with an extraordinarily wide range of substrate and partner proteins, but there is only limited structural information on these interactions. Extensive evidence on the flexibility of PDI in solution is not matched by any detailed picture of the scope of its motion. A new rapid method for simulating the motion of large proteins provides detailed molecular trajectories for PDI demonstrating extensive changes in the relative orientation of its four domains, great variation in the distances between key sites and internal motion within the core ligand-binding domain. The review shows that these simulations are consistent with experimental evidence and provide insight into the functional capabilities conferred by the extensive flexible motion of PDI.

Original languageEnglish
Pages (from-to)1383-1394
Number of pages12
JournalBiochimica Et Biophysica Acta-Proteins and Proteomics
Volume1865
Issue number11
DOIs
Publication statusPublished - 1 Nov 2017

Keywords

  • Endoplasmic reticulum
  • Oxidative protein folding
  • Protein disulfide isomerase
  • Protein dynamics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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    Freedman, R. B., Desmond, J. L., Byrne, L. J., Heal, J. W., Howard, M. J., Sanghera, N., Walker, K. L., Wallis, A. K., Wells, S. A., Williamson, R. A., & Römer, R. A. (2017). ‘Something in the way she moves’: The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI). Biochimica Et Biophysica Acta-Proteins and Proteomics, 1865(11), 1383-1394. https://doi.org/10.1016/j.bbapap.2017.08.014