Dry Molten Globule-Like Intermediates in Protein Folding, Function, and Disease

Area of Science:

• Biochemistry and Molecular Biology
• Protein Dynamics and Folding

Background:

• Protein performance relies on correct folding into a functional native state.
• Protein folding mechanisms are a key research area, studied for over 50 years.
• Wet molten globules (WMGs) are recognized unfolding intermediates, but dry molten globules (DMGs) are less understood.

Purpose of the Study:

• To consolidate existing literature and present new evidence on dry molten globules (DMGs).
• To provide a comprehensive perspective on the prevalence and role of DMGs in protein folding.
• To discuss the implications of DMGs in protein function and disease.

Main Methods:

• Literature review synthesizing available data on DMGs.
• Analysis of experimental evidence, including studies using sensitive structural probes.
• Comparative discussion of DMG characteristics versus WMGs.

Main Results:

• DMGs are near-native states, making them challenging to detect with global structural probes.
• Evidence suggests DMGs are significant, though often overlooked, intermediates in protein folding pathways.
• The near-native structure of DMGs may influence protein function and disease pathology.

Conclusions:

• DMGs represent a critical, albeit elusive, intermediate state in protein folding.
• Further research into DMGs is essential for a complete understanding of protein folding, function, and related diseases.
• The universality and significance of DMGs warrant broader consideration in the field of protein science.