The repeat region of cortactin is intrinsically disordered in solution

Sci Rep. 2017 Dec 1;7(1):16696. doi: 10.1038/s41598-017-16959-1.

Abstract

The multi-domain protein, cortactin, contains a 37-residue repeating motif that binds to actin filaments. This cortactin repeat region comprises 6½ similar copies of the motif and binds actin filaments. To better understand this region of cortactin, and its fold, we conducted extensive biophysical analysis. Size exclusion chromatography with multi-angle light scattering (SEC-MALS) reveals that neither constructs of the cortactin repeats alone or together with the adjacent helical region homo-oligomerize. Using circular dichroism (CD) we find that in solution the cortactin repeats resemble a coil-like intrinsically disordered protein. Small-angle X-ray scattering (SAXS) also indicates that the cortactin repeats are intrinsically unfolded, and the experimentally observed radius of gyration (R g) is coincidental to that calculated by the program Flexible-Meccano for an unfolded peptide of this length. Finally, hydrogen-deuterium exchange mass spectrometry (HDX-MS) indicates that the domain contains limited hydrophobic core regions. These experiments therefore provide evidence that in solution the cortactin repeat region of cortactin is intrinsically disordered.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • Cortactin / chemistry*
  • Cortactin / metabolism
  • Deuterium Exchange Measurement
  • Mass Spectrometry
  • Protein Conformation, alpha-Helical
  • Protein Unfolding
  • Scattering, Small Angle
  • X-Ray Diffraction

Substances

  • Cortactin