Close identity of a pressure-stabilized intermediate with a kinetic intermediate in protein folding

• DOI: 10.1073/pnas.0630309100
• Publication Date: 2003-03-18T23:15:05Z
• Authors: Ryo Kitahara; Kazuyuki Akasaka
• Keywords: Models, Molecular; 0301 basic medicine; Protein Folding; Protein Conformation; Ubiquitin; In Vitro Techniques; Deuterium; Kinetics; 03 medical and health sciences; Drug Stability; Pressure; Thermodynamics; Nuclear Magnetic Resonance, Biomolecular; Hydrogen

Atomic detailed structural study of a transiently existing folding intermediate is severely limited because of its short life. In ubiquitin, we found that a pressure-stabilized equilibrium conformer shares a common structural feature with the proline-trapped kinetic intermediate found in a pulse-labeling 1 H/ 2 H exchange NMR study [Briggs, M. S. & Roder, H. (1992) Proc. Natl. Acad. Sci. USA 89, 2017–2021]. The conformer is locally unfolded in the entire segment from residues 33 to 42 and in C-terminal residues 70–76. The close structural identity of an equilibrium intermediate stabilized under pressure with a transiently observed folding intermediate is likely to be general in terms of a folding funnel common to both experiments.