‘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

7 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

Fingerprint

Protein Disulfide-Isomerases
Protein folding
Molecular Chaperones
Protein Folding
Isomerization
Endoplasmic Reticulum
Disulfides
Oxidation-Reduction
Proteins
Trajectories
Ligands
Catalysts
Substrates

Keywords

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

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

‘Something in the way she moves’ : The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI). / Freedman, Robert B.; Desmond, Jasmine L.; Byrne, Lee J.; Heal, Jack W.; Howard, Mark J.; Sanghera, Narinder; Walker, Kelly L.; Wallis, A. Katrine; Wells, Stephen A.; Williamson, Richard A.; Römer, Rudolf A.

In: Biochimica Et Biophysica Acta-Proteins and Proteomics, Vol. 1865, No. 11, 01.11.2017, p. 1383-1394.

Research output: Contribution to journalReview article

Freedman, RB, Desmond, JL, Byrne, LJ, Heal, JW, Howard, MJ, Sanghera, N, Walker, KL, Wallis, AK, Wells, SA, Williamson, RA & Römer, RA 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, vol. 1865, no. 11, pp. 1383-1394. https://doi.org/10.1016/j.bbapap.2017.08.014
Freedman, Robert B. ; Desmond, Jasmine L. ; Byrne, Lee J. ; Heal, Jack W. ; Howard, Mark J. ; Sanghera, Narinder ; Walker, Kelly L. ; Wallis, A. Katrine ; Wells, Stephen A. ; Williamson, Richard A. ; Römer, Rudolf A. / ‘Something in the way she moves’ : The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI). In: Biochimica Et Biophysica Acta-Proteins and Proteomics. 2017 ; Vol. 1865, No. 11. pp. 1383-1394.
@article{cf78096dfe024508a6e49e87ffa72631,
title = "‘Something in the way she moves’: The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI)",
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.",
keywords = "Endoplasmic reticulum, Oxidative protein folding, Protein disulfide isomerase, Protein dynamics",
author = "Freedman, {Robert B.} and Desmond, {Jasmine L.} and Byrne, {Lee J.} and Heal, {Jack W.} and Howard, {Mark J.} and Narinder Sanghera and Walker, {Kelly L.} and Wallis, {A. Katrine} and Wells, {Stephen A.} and Williamson, {Richard A.} and R{\"o}mer, {Rudolf A.}",
year = "2017",
month = "11",
day = "1",
doi = "10.1016/j.bbapap.2017.08.014",
language = "English",
volume = "1865",
pages = "1383--1394",
journal = "Biochimica Et Biophysica Acta-Proteins and Proteomics",
issn = "1570-9639",
publisher = "Elsevier",
number = "11",

}

TY - JOUR

T1 - ‘Something in the way she moves’

T2 - The functional significance of flexibility in the multiple roles of protein disulfide isomerase (PDI)

AU - Freedman, Robert B.

AU - Desmond, Jasmine L.

AU - Byrne, Lee J.

AU - Heal, Jack W.

AU - Howard, Mark J.

AU - Sanghera, Narinder

AU - Walker, Kelly L.

AU - Wallis, A. Katrine

AU - Wells, Stephen A.

AU - Williamson, Richard A.

AU - Römer, Rudolf A.

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

KW - Endoplasmic reticulum

KW - Oxidative protein folding

KW - Protein disulfide isomerase

KW - Protein dynamics

UR - http://www.scopus.com/inward/record.url?scp=85029085603&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1016/j.bbapap.2017.08.014

U2 - 10.1016/j.bbapap.2017.08.014

DO - 10.1016/j.bbapap.2017.08.014

M3 - Review article

AN - SCOPUS:85029085603

VL - 1865

SP - 1383

EP - 1394

JO - Biochimica Et Biophysica Acta-Proteins and Proteomics

JF - Biochimica Et Biophysica Acta-Proteins and Proteomics

SN - 1570-9639

IS - 11

ER -