An integrated approach of NMR experiments and MD simulations visualizes structural dynamics of a cyclic multi-domain protein.

ABSTRACT: Cyclization can stabilize the structure of proteins, as previously demonstrated in single-domain proteins. Although Lys48-linked polyubiquitin, a multi-domain protein, is also known to be cyclized in human cells, the structural effects of cyclization remain unclear. Here, we examined the impact of cyclization on the structural stability and dynamics of cyclic Lys48-linked diubiquitin (Ub₂ ). As expected, cyclization increased the thermal stability of Ub₂ and its resistance to proteolytic digestion, indicating that cyclization stabilized the structure of Ub₂ . Furthermore, cyclization repressed the interdomain motion in Ub₂ , but cyclic Ub₂ still exhibited microsecond conformational exchange in NMR relaxation dispersion experiments. A s

SUBMITTER: Sorada T 

PROVIDER: S-EPMC10503408 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature