Viral Receptor-Binding Protein Evolves New Function through Mutations That Cause Trimer Instability and Functional...

Area of Science:

• Evolutionary biology
• Molecular biology
• Biochemistry

Background:

• Protein mutations conferring new activity often decrease stability.
• Instability was traditionally viewed as a detrimental cost of protein evolution.
• Recent evidence suggests unstable conformations may facilitate evolutionary transitions.

Purpose of the Study:

• To investigate if protein instability can potentiate the evolution of new protein activity.
• To examine the role of instability in the host-range evolution of a bacteriophage receptor-binding protein.

Main Methods:

• Comparative analysis of bacteriophage lambda receptor-binding protein before and after host-range evolution.
• Structural modeling to predict conformational changes.
• In vitro oligomeric state analysis to assess protein stability and interactions.

Main Results:

• The evolved receptor-binding protein is less stable than the ancestral form.
• Instability is linked to mutations disrupting protein trimer formation.
• The evolved protein may adopt multiple conformations with distinct receptor preferences.

Conclusions:

• Protein instability, particularly in receptor-binding proteins, may play a crucial role in viral host-range expansion.
• This challenges the conventional view of instability as solely deleterious in protein evolution.
• Unstable protein conformations could be key mediators of adaptive evolution in viruses.