Helix formation and the unfolded state of a 52-residue helical protein

Wei Cao, Clay Bracken, Neville R. Kallenbach, Min Lu

Research output: Contribution to journalArticlepeer-review


A growing class of proteins in biological processes has been found to be unfolded on isolation under normal solution conditions. We have used NMR spectroscopy to characterize the structural and dynamic properties of the unfolded and partially folded states of a 52-residue alanine-rich protein (Ala-14) at temperatures from -5°C to 40°C. At 40°C, alanine residues in Ala-14 adopt φ and ψ angles, consistent with a significant ensemble population of polyproline II conformation. Analysis of relaxation rates in the protein reveals that a series of residues, Gln 35-Ala 36-Ala 37-Lys 38-Asp 39-Asp 40-Ala 41-Ala 42, displays slow motional dynamics at both -5°C and 40°C. Temperature-dependent chemical shift changes indicate that this region is the site of helix initiation. The remaining N-terminal residues become increasingly dynamic as they extend from the nucleation site. The C terminus remains dynamic and changes less with temperature, indicating it is relatively unstructured. Ala-14 provides a high-resolution portrait of the unfolded state and the process of helix nucleation and propagation in the absence of tertiary contacts, information that bears on early events in protein folding.

Original languageEnglish (US)
Pages (from-to)177-189
Number of pages13
JournalProtein Science
Issue number1
StatePublished - Jan 2004


  • Helix formation
  • NMR
  • Protein folding
  • Protein structure
  • Unstructured proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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