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Foto på Anders Irbäck

Anders Irbäck

Professor

Foto på Anders Irbäck

Stability and Local Unfolding of SOD1 in the Presence of Protein Crowders

Författare

  • Anna Bille
  • Kristine Steen Jensen
  • Sandipan Mohanty
  • Mikael Akke
  • Anders Irbäck

Summary, in English

Using NMR and Monte Carlo (MC) methods, we investigate the stability and dynamics of superoxide dismutase 1 (SOD1) in homogeneous crowding environments, where either bovine pancreatic trypsin inhibitor (BPTI) or the B1 domain of streptococcal protein G (PGB1) serves as a crowding agent. By NMR, we show that both crowders, and especially BPTI, cause a drastic loss in the overall stability of SOD1 in its apo monomeric form. Additionally, we determine chemical shift perturbations indicating that SOD1 interacts with the crowder proteins in a residue-specific manner that further depends on the identity of the crowding protein. Furthermore, the specificity of SOD1-crowder interactions is reciprocal: chemical shift perturbations on BPTI and PGB1 identify regions that interact preferentially with SOD1. By MC simulations, we investigate the local unfolding of SOD1 in the absence and presence of the crowders. We find that the crowders primarily interact with the long flexible loops of the folded SOD1 monomer. The basic mechanisms by which the SOD1 β-barrel core unfolds remain unchanged when adding the crowders. In particular, both with and without the crowders, the second β-sheet of the barrel is more dynamic and unfolding-prone than the first. Notably, the MC simulations (exploring the early stages of SOD1 unfolding) and the NMR experiments (under equilibrium conditions) identify largely the same set of PGB1 and BPTI residues as prone to form SOD1 contacts. Thus, contacts stabilizing the unfolded state of SOD1 in many cases appear to form early in the unfolding reaction.

Avdelning/ar

  • Beräkningsbiologi och biologisk fysik - Genomgår omorganisation
  • Biofysikalisk kemi
  • eSSENCE: The e-Science Collaboration

Publiceringsår

2019

Språk

Engelska

Sidor

1920-1930

Publikation/Tidskrift/Serie

Journal of Physical Chemistry B

Volym

123

Issue

9

Dokumenttyp

Artikel i tidskrift

Förlag

The American Chemical Society (ACS)

Ämne

  • Other Physics Topics
  • Biophysics
  • Physical Chemistry

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1520-6106