Does protein unfolding play a functional role in vivo?

Area of Science:

• Biochemistry
• Structural Biology
• Biophysics

Background:

• Multidomain proteins are crucial for cellular functions.
• Their mechanical unfolding and refolding under force are increasingly recognized as vital mechanisms in vivo.
• This review focuses on the structural and functional implications of mechanical forces on these proteins.

Purpose of the Study:

• To explore the inherent properties of multidomain proteins under force.
• To characterize systems where mechanical unfolding is critical.
• To analyze how mechanical unfolding and refolding influence protein function.

Main Methods:

• Literature review of studies on multidomain proteins under mechanical force.
• Analysis of protein structure-function relationships in response to force.
• Characterization of key multidomain proteins in muscular contraction, cellular mechanotransduction, and bacterial adhesion.

Main Results:

• Multidomain proteins exhibit unique responses to force, including quantized responses, acting as molecular batteries, and delivering mechanical work via refolding.
• Mechanical unfolding influences elasticity, protects/exposes cryptic sites, and mediates binding-induced mechanical changes.
• Key proteins in muscular contraction, mechanotransduction, and bacterial adhesion demonstrate functional gains through mechanical processes.

Conclusions:

• Mechanical unfolding and refolding are fundamental to multidomain protein function.
• Understanding these mechanical properties is crucial for developing targeted therapies.
• Implications for designing mechano-active drugs against diseases like muscular dystrophy and cancer, and for novel antibiotics.