Disorder transitions and conformational diversity cooperatively modulate biological function in proteins

Area of Science:

• Biochemistry
• Structural Biology
• Protein Science

Background:

• Protein biological function is intrinsically linked to structural variations between its different conformers.
• Intrinsically disordered proteins (IDPs) are a class of proteins lacking a stable tertiary structure, playing crucial roles in various cellular processes.

Purpose of the Study:

• To investigate how order-disordered transitions influence structural differences among protein conformers.
• To analyze the impact of ligand binding on the conformational diversity of IDPs.

Main Methods:

• Analysis of a large dataset comprising 745 intrinsically disordered proteins.
• Utilizing crystallographic data to derive and compare structural differences between protein conformers.
• Quantifying conformational diversity and identifying order-disordered transitions.

Main Results:

• Approximately 50% of the studied proteins exhibited no significant order-disordered transitions, displaying low conformational diversity.
• The remaining 50% of proteins showed transitions and higher conformational diversity.
• Within the subset exhibiting transitions, 60% became more ordered upon ligand binding, while 40% became more disordered.

Conclusions:

• Order-disordered transitions significantly contribute to the conformational diversity of intrinsically disordered proteins.
• Ligand binding can induce substantial changes in protein order, influencing conformational heterogeneity.
• These findings suggest that structure-function relationships in IDPs are modulated by their dynamic transitions between ordered and disordered states.