4월14일(목)대학원세미나 Prof. Seokhee Kim(Department of Chemistry, Seoul National University, Korea)

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초청강사 Prof. Seokhee Kim
소속 Department of Chemistry, Seoul National University, Korea
일시 2016년 4월 14일(목) 오후5시
장소 아산이학관 331

 

 

“Activity control of a bacterial protease in periplasm”

 

 

 

Degradation of toxic misfolded proteins is an essential process for all types of cells. Proteases in protein quality control (PQC) are responsible for this function, which may require proper control of activity, because the uncontrolled proteolysis can be wasteful or cytotoxic. How the PQC proteases regulate their activity has been largely unknown. DegP is the major PQC protease in bacterial periplasm and belongs to the highly conserved HtrA family, whose members are associated with pathogenesis of various bacteria. Here I present that distinct self-regulatory elements in architecture control DegP proteolysis and maintain the cellular fitness during misfolded protein stress in vivo. Biochemical, biophysical, and structural studies revealed mechanisms of activity regulation; the bipartite mode of substrate binding, dynamic conversion between inactive and active states, and the assembly of large cages. Mutations that modify these molecular transformations could generate a rogue protease that kills cells by excessive proteolysis and this lethality could be suppressed by new intragenic mutations that offset the original mutational effect or a mutant lipoprotein that functions as a novel inhibitor. These results demonstrate that there is a delicate balance of quality control proteolysis in bacterial periplasm, suggesting that its disruption either by inhibition or activation of DegP may be a good strategy for antibiotic development.


20160414_세미나_Prof. Seokhee Kim.hwp