Denatured states of low-complexity polypeptide sequences differ dramatically from those of foldable sequences

Franco O. Tzul, Bruce E. Bowler

Research output: Contribution to journalArticlepeer-review

Abstract

How the primary sequence of a protein encodes conformational preferences that operate early in folding to promote efficient formation of the correct native topology is still poorly understood. To address this issue, we have prepared a set of yeast iso-1-cytochrome c variants that contain polyalanine inserts ranging from 6 to 30 residues in length near the N terminus of the protein. We study the thermodynamics and kinetics of His-heme loop formation in the denatured state at 3 and 6 M guanidine-HCl concentration. We find that polyalanine closely approximates a random coil with excluded volume giving scaling exponents, ν3, for equilibrium loop formation of 2.26 ± 0.13 and 1.97 ± 0.04 in 3 and 6 M guanidine-HCl, respectively. The rate of loop breakage initially decreases and then becomes independent of loop size as would be expected for a random coil. Comparison with previously reported data for denatured state His-heme loop formation for iso-1-cytochrome c and Rhodopseudomonas palustris cytochrome c′, shows that foldable sequences deviate significantly from random coil behavior and that the deviation is fold-dependent.

Original languageEnglish
Pages (from-to)11364-11369
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number25
DOIs
StatePublished - Jun 22 2010

Keywords

  • Chain stiffness
  • Protein folding
  • Residual structure

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