Protein folding and binding can emerge as evolutionary spandrels through structural coupling.

Area of Science:

• Biophysics
• Evolutionary Biology
• Molecular Biology

Background:

• Protein interactions are crucial for cellular functions like metabolism and signaling.
• Protein evolution is influenced by folding stability, especially under environmental changes.
• The interplay between protein folding and binding is a key factor in evolutionary constraints.

Purpose of the Study:

• To investigate the evolutionary coupling between protein folding stability and binding strength.
• To understand how structural coupling between folding and binding influences protein trait evolution.
• To explore the emergence of evolutionary spandrels in protein traits.

Main Methods:

• Utilized a combined biophysical and evolutionary modeling approach.
• Analyzed the emergence of protein traits without intrinsic fitness advantage.
• Examined evolutionary paths for proteins with both functional binding and deleterious misfolding.

Main Results:

• Protein traits like folding stability and binding strength can evolve as spandrels, even without direct fitness benefits.
• Proteins may evolve strong, non-functional binding interactions to enhance folding stability when misfolding is detrimental.
• Evolutionary trajectories for proteins with functional binding and misfolding risks are constrained, favoring stability gains before binding optimization.

Conclusions:

• The structural coupling between folding and binding explains the evolution of seemingly non-functional protein interactions.
• Understanding these evolutionary spandrels provides insights into protein evolution under selective pressures.
• Findings have implications for both natural protein evolution and the engineering of novel proteins.