Dual binding mode in cohesin-dockerin complexes as assessed through stretching studies

Area of Science:

• Biophysics
• Structural Biology
• Computational Biology

Background:

• Experimental studies identified two force-displacement patterns ('short' and 'long') during the stretching of wild-type (WT) cohesin-dockerin complexes.
• This duality was previously attributed to two distinct binding modes within the complex.

Purpose of the Study:

• To theoretically investigate the separation mechanisms of cohesin-dockerin complexes from *C. thermocellum*.
• To determine if binding orientation, rather than distinct binding types, can explain the observed dual stretching patterns.

Main Methods:

• Utilized a coarse-grained structure-based model to simulate the stretching of cohesin-dockerin complexes.
• Simulations were performed at pulling speeds comparable to experimental conditions.
• Analyzed the unravelling pathways of wild-type (PDB:1OHZ) and mutated (PDB:2CCL) *C. thermocellum* complexes, and a *R. flavefaciens* complex (PDB:4IU3).

Main Results:

• The WT *C. thermocellum* complex demonstrated two distinct unravelling pathways, consistent with experimental 'short' and 'long' patterns.
• The mutated complex exclusively produced 'short' trajectories, suggesting the role of native binding orientation.
• Similar 'short' and 'long' pathways were observed in the *R. flavefaciens* cohesin-dockerin-Xmodule complex.

Conclusions:

• The duality in stretching patterns observed during cohesin-dockerin complex separation can arise from different binding orientations within the complex.
• This finding challenges the necessity of invoking distinct binding types to explain the experimental duality.
• The study provides a theoretical framework supporting the influence of molecular orientation on complex mechanical properties.