Cohesin-dockerin code in cellulosomal dual binding modes and its allosteric regulation by proline isomerization

Area of Science:

• Biochemistry
• Biotechnology
• Molecular Biology

Background:

• Cellulose is a globally abundant, renewable feedstock for biofuels and chemicals.
• Cellulosomes are large, efficient multi-enzyme complexes that degrade lignocellulosic biomass.
• The structure and dynamics of cellulosome assembly are crucial for their function.

Purpose of the Study:

• To investigate the binding modes and dynamics of cohesin-dockerin interactions in cellulosomes.
• To elucidate the regulatory mechanisms governing cellulosome structural plasticity.
• To understand the role of proline isomerization in cellulosome assembly and function.

Main Methods:

• Single-molecule fluorescence resonance energy transfer (smFRET) to detect binding mode distributions.
• Molecular simulations to model cohesin-dockerin pair interactions.
• Analysis of proline residue isomerization effects on binding kinetics.

Main Results:

• Direct detection of varying distributions between two proposed cohesin-dockerin binding modes.
• Identification of a cohesin-dockerin code dictating binding mode preferences.
• Discovery of prolyl isomerase-mediated allosteric control via proline isomerization, regulating binding dynamics.

Conclusions:

• Cellulosome binding modes are not static but dynamically regulated by an intrinsic code.
• Prolyl isomerase acts as a key regulator of cellulosome structure and function through allosteric control.
• This study provides new mechanistic insights into the plasticity and dynamics of cellulosome complexes for biomass degradation.