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Probing the mechanism of cellulosome attachment to the Clostridium thermocellum cell surface: computer simulation of the Type II Cohesin-Dockerin complex and its variants

Journal Article · · Protein Engineering Design and Selection
The recalcitrance of lignocellulosic biomass to hydrolysis is the bottleneck in cellulosic ethanol production. Efficient degradation of biomass by the anaerobic bacterium Clostridium thermocellum is carried out by the multicomponent cellulosome complex. The bacterial cell-surface attachment of the cellulosome is mediated by high-affinity protein-protein interactions between the Type II cohesin domain borne by the cell envelope protein and the Type II dockerin domain, together with neighboring X-module present at the C-terminus of the scaffolding protein (Type II coh-Xdoc). Here, the Type II coh-Xdoc interaction is probed using molecular dynamics simulations, free-energy calculations and essential dynamics analyses on both the wild type and various mutants of the C. thermocellum Type II coh-Xdoc in aqueous solution. The simulations identify the hot spots, i.e. the amino acid residues that may lead to a dramatic decrease in binding affinity upon mutation and also probe the effects of mutations on the mode of binding. The results suggest that bulky and hydrophobic residues at the protein interface, which make specific contacts with their counterparts, may play essential roles in retaining a rigid cohesin-dockerin interface. Moreover, dynamical cross-correlation analysis indicates that the X-module has a dramatic effect on the cohesin-dockerin interaction and is required for the dynamical integrity of the interface.
Research Organization:
Oak Ridge National Laboratory (ORNL)
Sponsoring Organization:
ORNL Program Development
DOE Contract Number:
AC05-00OR22725
OSTI ID:
1017385
Journal Information:
Protein Engineering Design and Selection, Journal Name: Protein Engineering Design and Selection Journal Issue: 10 Vol. 23; ISSN 1741-0126
Country of Publication:
United States
Language:
English