Structural basis for effector protein recognition by the Dot/Icm Type IVB coupling protein complex

Area of Science:

• Microbiology
• Structural Biology
• Molecular Biology

Background:

• Legionella pneumophila utilizes the Dot/Icm type IVB secretion system (T4BSS) to translocate approximately 300 effector proteins into host cells.
• The Dot/Icm type IVB coupling protein (T4CP) complex, comprising IcmS, IcmW, and LvgA, is crucial for the selective export of specific effector subclasses.

Purpose of the Study:

• To elucidate the structural basis of effector recognition by the Dot/Icm T4CP complex.
• To investigate the substrate-binding specificities of the LvgA subunit within the T4CP complex.

Main Methods:

• X-ray crystallography was employed to determine the structure of a T4CP subcomplex bound to the effector protein VpdB.
• Mutational analyses were performed to identify and characterize effector binding motifs recognized by LvgA.

Main Results:

• The crystal structure revealed a direct interaction between LvgA and a C-terminal linear motif of the effector VpdB.
• LvgA's binding interface was found to interact with the C-terminal regions of three additional effectors: SidH, SetA, and PieA.
• Mutational studies identified a shared FxxxLxxxK binding motif in VpdB and SidH, indicating LvgA recognizes multiple distinct binding motifs.

Conclusions:

• This study provides a structural foundation for understanding how the Dot/Icm T4CP complex recognizes and binds to its diverse effector substrates.
• The findings highlight the adaptable substrate-binding capabilities of the LvgA adaptor subunit, essential for the T4BSS's functional versatility.