The structure in solution of the b domain of protein disulfide isomerase

J Kemmink*, K Dijkstra, M Mariani, RM Scheek, E Penka, M Nilges, NJ Darby

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

67 Citations (Scopus)

Abstract

Protein disulfide isomerase (PDI) is a multifunctional protein of the endoplasmic reticulum, which catalyzes the formation, breakage and rearrangement of disulfide bonds during protein folding. It consists of four domains designated a, b, b' and a'. Both a and a' domains contain an active site with the sequence motif -Cys-Gly-His-Cys-involved directly in thiol-disulfide exchange reactions. As expected these domains have structures very similar to the ubiquitous redox protein thioredoxin. A low-resolution NMR structure of the b domain revealed that this domain adopts a fold similar to the PDI a domain and thioredoxin [Kemmink, J., Darby, N.J., Dijkstra, K., Nilges, M. and Creighton, T.E. (1997) Gun: Biol., 7, 239-245]. A refined ensemble of solution structures based on the input of 1865 structural restraints shows that the structure of PDI b is well defined throughout the complete protein except for about 10 residues at the C-terminus of the sequence. N-15 relaxation data show that these residues are disordered and not part of this structural domain. Therefore the domain boundaries of PDI can now be fixed with reasonable precision. Structural comparison of the PDI b domain with thioredoxin and PDI a reveals several features important for thiol-disulfide exchange activity.

Original languageEnglish
Pages (from-to)357-368
Number of pages12
JournalJournal of Biomolecular Nmr
Volume13
Issue number4
Publication statusPublished - Apr-1999

Keywords

  • calsequestrin
  • disulfide bond
  • protein disulfide isomerase
  • protein folding
  • thioredoxin
  • THIOREDOXIN-LIKE DOMAINS
  • AMBIGUOUS DISTANCE RESTRAINTS
  • CORRELATION NMR-SPECTROSCOPY
  • TRIPLE-RESONANCE NMR
  • NF-KAPPA-B
  • C-13-LABELED PROTEINS
  • LARGER PROTEINS
  • SENSITIVITY IMPROVEMENT
  • CYSTEINE RESIDUES
  • ESCHERICHIA-COLI

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