β-sheet folding mechanisms from perturbation energetics

Songpon Deechongkit, Houbi Nguyen, Marcus Jager, Evan T. Powers, Martin Gruebele, Jeffery W. Kelly

Research output: Contribution to journalReview article

Abstract

Amide backbone and sidechain mutagenesis data can be used in combination with kinetic and thermodynamic measurements to understand the energetic contributions of backbone hydrogen bonding and the hydrophobic effect to the acquisition of β-sheet structure. For example, it has been revealed that loop 1 of the WW domain forms in the transition state, consistent with the emerging theme that reverse turn formation is rate limiting in β-sheet folding. A distinct subset of WW domain residues principally influences thermodynamic stability by forming hydrogen bonds and hydrophobic interactions that stabilize the native state. Energetic data and sequence mining reveal that only a small subset of the molecular information contained in sequences or observed in high-resolution structures is required to generate folded functional β-sheets, consistent with evolutionary robustness.

Original languageEnglish (US)
Pages (from-to)94-101
Number of pages8
JournalCurrent Opinion in Structural Biology
Volume16
Issue number1
DOIs
StatePublished - Feb 1 2006

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ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology

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