Backbone chemical shift assignment and dynamics of the N-terminal domain of ClpB from Francisella tularensis type VI secretion system

Ameeq Ul Mushtaq,Athar Alam,Anders Sjöstedt,Gerhard Gröbner,Jörgen Ådén

doi:10.1007/s12104-021-10062-3

Abstract

The Hsp100 family member ClpB is a protein disaggregase which solubilizes and reactivates stress-induced protein aggregates in cooperation with the DnaK/Hsp70 chaperone system. In the pathogenic bacterium Francisella tularensis, ClpB is involved in type VI secretion system (T6SS) disassembly through depolymerization of the IglA-IglB sheath. This leads to recycling and reassembly of T6SS components and this process is essential for the virulence of the bacterium. Here we report the backbone chemical shift assignments and 15N relaxation-based backbone dynamics of the N-terminal substrate-binding domain of ClpB (1-156).

Highlights

ClpB is a member of ring-forming AAA + family ATPases that cooperates together with the DnaK/Hsp70 system to reactivate stress-denatured aggregated proteins
Besides its role in solubilizing stress-induced protein aggregates, a role of ClpB in type VI secretion (T6S) has recently been reported in the highly pathogenic intracellular bacterium Francisella tularensis that infects and replicates mainly inside macrophages and causes the disease tularemia in a large number of mammalian species (Brodmann et al 2017; Alam et al 2020)
A recent report suggests that ClpB apparently serves as a functional homolog of ClpV and it harnesses energy generated by the hydrolysis of ATPs and it is required for depolymerization of the T6SS sheath and the subsequent recycling and reassembly of the T6SS components

Summary

Introduction

ClpB is a member of ring-forming AAA + family ATPases that cooperates together with the DnaK/Hsp70 system to reactivate stress-denatured aggregated proteins. Keywords NMR resonance assignment · 15N relaxation · ClpB chaperone · Type VI secretion system · Francisella tularensis We present the backbone chemical shift assignments and dynamics of the N-terminal substrate binding domain of ClpB (1-156) that binds to the IglA-IglB sheath which is important for recycling and reassembly, and essential for the virulence of the bacterium, and can be a potential drug target.

Results

Conclusion