Principal Investigator_A.Kidera
Post-translational modification by polyubiquitin chain: its structure, dynamics, and function
Akinori Kidera
Professor, Structural Bioinformatics
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Our Aim
Polyubiquitin chains, polymer of ubiquitins attached to a protein, have distinct functions determined by each different ubiquitin linkage. We try to elucidate at the atomic level the correlation between the linkages and the function.
Background
Protein ubiquitination is a post-translational modification involved in the regulation of diverse cellular processes, including protein degradat ion, cel l signal ing and DNA damage response. Disturbance of the ubiquitin system causes serious diseases such as cancers and neurodegenerative diseases. Various types of ubiqutin modification are possible and observed experimentally. These different modes of ubiquitination are considered to control the respective functions. However, the underlying mechanism remains unclear.
Research Overview
In the present study, we perform molecular dynamics simulations of polyubiquitin chains with different linkages, and investigate their conformations and dynamics to elucidate the atomic mechanism of their specific functions.
Achievements
We focused on K48-, K63-, and K11-linked diubiquitins, which are formed by linking two ubiquitins and the minimum-length polyubiquitin chains, and performed their molecular dynamics simulations in explicit water. The results showed that the diubiquitins are so flexible that they are different from their crystal structures, and temporal interactions are observed between ubiquitins. These semistable conformations reveal differences and specificities in these diubiquitins.