Structural heterogeneity in microcrystalline ubiquitin studied by solid-state NMR

Protein Sci. 2015 May;24(5):592-8. doi: 10.1002/pro.2654. Epub 2015 Mar 16.

Abstract

By applying [1-(13) C]- and [2-(13) C]-glucose labeling schemes to the folded globular protein ubiquitin, a strong reduction of spectral crowding and increase in resolution in solid-state NMR (ssNMR) spectra could be achieved. This allowed spectral resonance assignment in a straightforward manner and the collection of a wealth of long-range distance information. A high precision solid-state NMR structure of microcrystalline ubiquitin was calculated with a backbone rmsd of 1.57 to the X-ray structure and 1.32 Å to the solution NMR structure. Interestingly, we can resolve structural heterogeneity as the presence of three slightly different conformations. Structural heterogeneity is most significant for the loop region β1-β2 but also for β-strands β1, β2, β3, and β5 as well as for the loop connecting α1 and β3. This structural polymorphism observed in the solid-state NMR spectra coincides with regions that showed dynamics in solution NMR experiments on different timescales.

Keywords: 13C sparse labeling; dynamics; heterogeneity; solid-state NMR; ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular*
  • Protein Folding
  • Protein Structure, Secondary*
  • Solutions / chemistry
  • Ubiquitin / chemistry*

Substances

  • Solutions
  • Ubiquitin

Associated data

  • PDB/2MSG