Automatic assignment of the intrinsically disordered protein Tau with 441-residues

J Am Chem Soc. 2010 Sep 1;132(34):11906-7. doi: 10.1021/ja105657f.

Abstract

Intrinsically disordered proteins carry out many important functions in the cell. However, the lack of an ordered structure causes dramatic signal overlap and complicates the NMR-based characterization of their structure and dynamics. Here we demonstrate that the resonance assignment of 441-residue Tau and its smaller isoforms, htau24 (383 residues) and htau23 (352 residues), three prototypes of intrinsically disordered proteins, which bind to microtubules and play a key role in Alzheimer disease, can be obtained within 5 days by a combination of seven-dimensional NMR spectra with optimized methods for automatic assignment. Chemical shift differences between the three isoforms provide evidence for the global folding of Tau in solution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Computational Biology
  • Databases, Protein
  • Electronic Data Processing*
  • Humans
  • Magnetic Resonance Spectroscopy / standards
  • Protein Conformation
  • Protein Isoforms / chemistry
  • Reference Standards
  • tau Proteins / chemistry*

Substances

  • Protein Isoforms
  • tau Proteins