Protein structure-function continuum model: Emerging nexuses between specificity, evolution, and structure.

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• The traditional binary of protein structure-function is being replaced by a trinity including disorder.
• Protein intrinsic disorder plays a critical role in various biological processes.

Purpose of the Study:

• To review the importance of intrinsic disorder in protein function.
• To discuss how a continuum model integrating structure and disorder enhances understanding of protein functionality, specificity, and evolution.

Main Methods:

• Literature review and synthesis of current research on protein structure, disorder, and function.
• Analysis of the continuum model's applicability to various biological phenomena.

Main Results:

• The continuum model effectively incorporates conformational flexibility and intrinsic disorder.
• Intrinsic disorder is crucial for protein-protein interactions, regulatory processes, and membrane-less organelle formation.
• The model offers insights into moonlighting proteins, amyloids, prions, infectious diseases, and protein function under extreme conditions.

Conclusions:

• The integration of structure and disorder under a single continuum model provides a clearer framework for understanding proteins.
• This revised paradigm is essential for advancing our knowledge of molecular mechanisms and protein evolution.