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Specialized iNANO Lecture: Moving in Circles: Dynamics of processivity clamp proteins

Penny Beuning, Chemistry and Chemical Biology, Northwestern University, Boston, USA

2019.10.09 | Trine Møller Hansen

Date Thu 31 Oct
Time 11:15 12:00
Location iNANO 1590-213, Gustav Wieds Vej 14, 8000 Aarhus C

Professor Penny Beuning, Chemistry and Chemical Biology, Northwestern University, Boston, USA

Moving in Circles: Dynamics of processivity clamp proteins

The relationship between protein dynamics and function is still poorly understood. The bacterial beta sliding clamp protein plays a central role in DNA replication and in coordinating activities on DNA. Whereas clamp proteins in higher organisms tend to be trimers, the bacterial beta clamp is a dimer. The beta sliding clamp displays dynamic behavior, particularly at the dimer interface, raising the possibility that the clamp spontaneously transiently opens.

We hypothesize that the intrinsic dynamics of the beta clamp regulates its functions in protein-protein and protein-DNA interactions. To test the role of dynamics in clamp function, we designed stabilizing and destabilizing mutations at and near the dimer interface. Beta clamp variants with destabilized dimer interfaces generally had altered thermal stability and dimerization and did not support bacterial growth. Molecular dynamics simulations indicate that variants with destabilizing mutations have dramatically altered hydrogen bonding patterns at the dimer interface. The effects of these mutations are now being tested in a beta variant that is covalently closed at one interface to determine the relative effects of dynamics at the two interfaces.

Host: Associate Professor Victoria Birkedal, iNANO & Dept. of Chemistry, AU

Specialized iNANO Lectures
4869 / i35