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

TitleCohesin-dockerin code in cellulosomal dual binding modes and its allosteric regulation by proline isomerization.
Publication TypeJournal Article
Year of Publication2021
AuthorsVera AManuel, Galera-Prat A, Wojciechowski M, Różycki B, Laurents DV, Carrión-Vázquez M, Cieplak M, Tinnefeld P
Date Published2021 Jun 03
KeywordsAllosteric Regulation, Bacterial Proteins, Binding Sites, Cell Cycle Proteins, Cellulosomes, Chromosomal Proteins, Non-Histone, Isomerism, Models, Molecular, Multienzyme Complexes, Peptidylprolyl Isomerase, Proline, Protein Binding, Protein Conformation, Single Molecule Imaging

Cellulose is the most abundant organic molecule on Earth and represents a renewable and practically everlasting feedstock for the production of biofuels and chemicals. Self-assembled owing to the high-affinity cohesin-dockerin interaction, cellulosomes are huge multi-enzyme complexes with unmatched efficiency in the degradation of recalcitrant lignocellulosic substrates. The recruitment of diverse dockerin-borne enzymes into a multicohesin protein scaffold dictates the three-dimensional layout of the complex, and interestingly two alternative binding modes have been proposed. Using single-molecule fluorescence resonance energy transfer and molecular simulations on a range of cohesin-dockerin pairs, we directly detect varying distributions between these binding modes that follow a built-in cohesin-dockerin code. Surprisingly, we uncover a prolyl isomerase-modulated allosteric control mechanism, mediated by the isomerization state of a single proline residue, which regulates the distribution and kinetics of binding modes. Overall, our data provide a novel mechanistic understanding of the structural plasticity and dynamics of cellulosomes.

Alternate JournalStructure
PubMed ID33561387