Structural basis of redox-dependent substrate binding of protein disulfide isomerase

Scientific Reports
Maho Yagi-UtsumiKoichi Kato

Abstract

Protein disulfide isomerase (PDI) is a multidomain enzyme, operating as an essential folding catalyst, in which the b' and a' domains provide substrate binding sites and undergo an open-closed domain rearrangement depending on the redox states of the a' domain. Despite the long research history of this enzyme, three-dimensional structural data remain unavailable for its ligand-binding mode. Here we characterize PDI substrate recognition using α-synuclein (αSN) as the model ligand. Our nuclear magnetic resonance (NMR) data revealed that the substrate-binding domains of PDI captured the αSN segment Val37-Val40 only in the oxidized form. Furthermore, we determined the crystal structure of an oxidized form of the b'-a' domains in complex with an undecapeptide corresponding to this segment. The peptide-binding mode observed in the crystal structure with NMR validation, was characterized by hydrophobic interactions on the b' domain in an open conformation. Comparison with the previously reported crystal structure indicates that the a' domain partially masks the binding surface of the b' domain, causing steric hindrance against the peptide in the reduced form of the b'-a' domains that exhibits a closed conformation. These findings pro...Continue Reading

References

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Citations

Mar 5, 2016·Brain Pathology·Louise Berkhoudt LassenPoul Henning Jensen
Jul 13, 2017·Chemical Reviews·Deborah Fass, Colin Thorpe
Jul 4, 2018·ELife·Ricardo Guerrero-FerreiraHenning Stahlberg
Jun 4, 2019·Biological & Pharmaceutical Bulletin·Maho Yagi-Utsumi
Aug 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Ekaterina I BiterovaLloyd W Ruddock
Aug 29, 2019·Scientific Reports·Valerio FerrarioJürgen Pleiss
Jan 6, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiahui FuDong Yang
Nov 7, 2020·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Lei WangChih-Chen Wang
Mar 5, 2017·Archives of Biochemistry and Biophysics·Razieh KaramzadehAli Akbar Moosavi-Movahedi
Jun 3, 2021·International Journal of Molecular Sciences·Panagiota Mavroeidi, Maria Xilouri
Aug 9, 2019·Biochemistry·Jessica GuyetteKen Teter

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Methods Mentioned

BETA
nuclear
small-angle neutron scattering
X-ray
NMR

Software Mentioned

HKL2000
MOLREP
COOT
REFMAC5
PROCHECK
PyMOL
SPARKY

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