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Measuring In Vitro ATPase Activity for Enzymatic Characterization
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The ATPases of the mycobacterial type VII secretion system: Structural and mechanistic insights into secretion

Thomas D Crosskey1, Katherine S H Beckham1, Matthias Wilmanns2

  • 1European Molecular Biology Laboratory, Hamburg Unit, Notkestrasse 85, 22607, Hamburg, Germany.

Progress in Biophysics and Molecular Biology
|November 26, 2019
PubMed

Insights

Mycobacterium tuberculosis (Mtb) uses the type VII secretion system (T7SS) to infect hosts. This review explores the roles of AAA+ ATPases EccA and EccC in protein translocation, offering potential targets for new tuberculosis drugs.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a leading infectious disease.
  • Mtb virulence relies on proteins secreted via the type VII secretion system (T7SS) into host cells.
  • The T7SS is a promising target for novel anti-TB drug and vaccine development.

Purpose of the Study:

  • To review the mechanism of protein translocation across mycobacterial membranes via the T7SS.
  • To explore the critical roles of AAA+ ATPases EccA and EccC in T7SS function.
  • To discuss the potential of targeting the T7SS, particularly its ATPases, for therapeutic strategies.

Main Methods:

  • Literature review focusing on the T7SS and its components.
  • Analysis of the known functions of AAA+ ATPases in protein secretion.
  • Comparative analysis with other bacterial secretion systems.

Main Results:

  • While T7SS components are known, the translocation mechanism remains unclear.
  • AAA+ ATPases EccA and EccC are crucial for protein translocation across mycobacterial membranes.
  • The T7SS lacks homology to other secretion systems, but ATPase involvement is a common theme.

Conclusions:

  • Understanding T7SS ATPase mechanisms is key to elucidating protein translocation.
  • Targeting the T7SS virulence factors presents a viable strategy for combating TB.
  • Further research into EccA and EccC functions could yield new therapeutic interventions against Mtb.
Keywords:
ATPaseBacterial virulenceMycobacteriaType VII secretion

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