Is there an en route folding intermediate for Cold shock proteins?

Area of Science:

• Biochemistry
• Molecular Biology
• Biophysics

Background:

• Cold shock proteins (Csps) are crucial for cellular response to cold stress across many organisms.
• Previous studies suggest a conserved two-state folding mechanism for Csps with a compact transition state (TS).
• Atomic-level understanding of the Csps folding pathway remains elusive.

Purpose of the Study:

• To elucidate the atomic details of the cold shock protein folding mechanism.
• To investigate the potential existence and characteristics of folding intermediates and transition states.

Main Methods:

• Utilized all-atom Go model-based simulations for detailed analysis.
• Employed P(fold) analysis to determine the transition state ensemble.

Main Results:

• Predicted an en route intermediate with ordered β strands 1-2-3 and near-complete β1-β4 contacts.
• This intermediate is likely too unstable for detection by prior experimental methods.
• The transition state ensemble was identified and found to be even more compact than the intermediate.

Conclusions:

• The folding of cold shock proteins involves a complex pathway with a transient, compact intermediate.
• The transition state is exceptionally compact, offering new insights into protein folding dynamics.
• These findings enhance our understanding of cold shock response mechanisms at the molecular level.