The Chlamydia pneumoniae effector SemD exploits its host's endocytic machinery by structural and functional mimicry

Area of Science:

• Microbiology
• Cell Biology
• Structural Biology

Background:

• Chlamydia pneumoniae is an obligate intracellular pathogen that invades host epithelial cells.
• Pathogen entry relies on secreted effector proteins that manipulate host cell machinery, particularly endocytosis.

Purpose of the Study:

• To elucidate the structural basis of Chlamydia pneumoniae effector SemD's interaction with host cell proteins.
• To understand how SemD facilitates pathogen internalization into host cells.

Main Methods:

• High-resolution structural determination of SemD via co-crystallization with host binding partners.
• Analysis of SemD's binding interactions and domain flexibility.

Main Results:

• SemD binds and activates the host actin regulator N-WASP by co-opting the Cdc42 binding site, bypassing the need for active Cdc42.
• SemD exhibits specificity, binding N-WASP strongly but not FMNL2.
• SemD possesses flexible and structured domains enabling simultaneous interaction with the host cell membrane, SNX9, and N-WASP.

Conclusions:

• SemD structurally hijacks the host endocytic system through specific interactions with host proteins.
• This mechanism allows for efficient internalization of Chlamydia pneumoniae into epithelial cells.