Solution Ensemble of the C-Terminal Domain from the Transcription Factor Pdx1 Resembles an Excluded Volume Polymer

Erik C. Cook, Debashish Sahu, Monique Bastidas, Scott A. Showalter

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The pancreatic and duodenal homeobox 1 (Pdx1) is an essential pancreatic transcription factor. The C-terminal intrinsically disordered domain of Pdx1 (Pdx1-C) has a heavily biased amino acid composition; most notably, 18 of 83 residues are proline, including a hexaproline cluster near the middle of the chain. For these reasons, Pdx1-C is an attractive target for structure characterization, given the availability of suitable methods. To determine the solution ensembles of disordered proteins, we have developed a suite of 13 C direct-detect NMR experiments that provide high spectral quality, even in the presence of strong proline enrichment. Here, we have extended our suite of NMR experiments to include four new pulse programs designed to record backbone residual dipolar couplings in a 13 C, 15 N-CON detection format. Using our NMR strategy, in combination with small-angle X-ray scattering measurements and Monte Carlo simulations, we have determined that Pdx1-C is extended in solution, with a radius of gyration and internal scaling similar to that of an excluded volume polymer, and a subtle tendency toward a collapsed structure to the N-terminal side of the hexaproline sequence. This structure leaves Pdx1-C exposed for interactions with trans-regulatory co-factors that contribute with Pdx1 to transcription control in the cell.

Original languageEnglish (US)
Pages (from-to)106-116
Number of pages11
JournalJournal of Physical Chemistry B
Issue number1
StatePublished - Oct 1 2019

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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