Structure and function of interacting IcmR-IcmQ domains from a type IVb secretion system in Legionella pneumophila

Suchismita Raychaudhury1, Jeremiah D Farelli, Timothy P Montminy

  • 1Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA 02118-2526, USA.

Insights

Legionella pneumophila uses IcmQ to form a vacuole for replication. The protein IcmR inhibits IcmQ

Area of Science:

  • Microbiology
  • Cell Biology
  • Structural Biology

Background:

  • Legionella pneumophila infection relies on vacuole formation.
  • The Type IVb secretion system (T4bSS) is essential for vacuole biogenesis.
  • IcmQ is a key T4bSS component interacting with IcmR.

Purpose of the Study:

  • To elucidate the structural and functional roles of IcmQ and its interaction with IcmR.
  • To understand the mechanism of membrane association and permeabilization by IcmQ.
  • To provide insights into IcmR-mediated regulation of IcmQ.

Main Methods:

  • Protein domain analysis (N-terminal Qn, C-terminal domain, basic linker).
  • Biochemical assays for self-dimerization and membrane association/permeabilization.
  • Crystal structure determination of Qn in complex with IcmR.

Main Results:

  • The N-terminal domain (Qn) of IcmQ mediates self-dimerization.
  • The C-terminal domain and basic linker promote membrane association.
  • IcmR binding inhibits IcmQ self-dimerization and membrane permeabilization but not membrane binding.
  • Crystal structures reveal a four-helix bundle interaction between Qn and IcmR.

Conclusions:

  • IcmQ self-dimerization and membrane permeabilization are regulated by IcmR.
  • Structural data provides models for IcmQ-mediated membrane permeabilization.
  • Insights into interspecies IcmQ-IcmR interactions in Legionella.

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