8S5T

Structure of SemD in complex

Summary for 8S5T

• Entry DOI: 10.2210/pdb8s5t/pdb
• Descriptor: Effector SemD, Neural Wiskott-Aldrich syndrome protein (2 entities in total)
• Functional Keywords: effector protein, endocytosis
• Biological source: Chlamydia; More
• Total number of polymer chains: 2
• Total formula weight: 45682.05

Authors

Kocher, F.,Applegate, V.,Port, A.,Reiners, J.,Spona, D.,Haensch, S.,Smits, S.H.,Hegemann, J.,Moelleken, K. (deposition date: 2024-02-25, release date: 2024-08-07, Last modification date: 2025-02-19)

Primary citation

Kocher, F.,Applegate, V.,Reiners, J.,Port, A.,Spona, D.,Hansch, S.,Mirzaiebadizi, A.,Ahmadian, M.R.,Smits, S.H.J.,Hegemann, J.H.,Molleken, K.
The Chlamydia pneumoniae effector SemD exploits its host's endocytic machinery by structural and functional mimicry.
Nat Commun, 15:7294-7294, 2024

PubMed Abstract: To enter epithelial cells, the obligate intracellular pathogen Chlamydia pneumoniae secretes early effector proteins, which bind to and modulate the host-cell's plasma membrane and recruit several pivotal endocytic host proteins. Here, we present the high-resolution structure of an entry-related chlamydial effector protein, SemD. Co-crystallisation of SemD with its host binding partners demonstrates that SemD co-opts the Cdc42 binding site to activate the actin cytoskeleton regulator N-WASP, making active, GTP-bound Cdc42 superfluous. While SemD binds N-WASP much more strongly than Cdc42 does, it does not bind the Cdc42 effector protein FMNL2, indicating effector protein specificity. Furthermore, by identifying flexible and structured domains, we show that SemD can simultaneously interact with the membrane, the endocytic protein SNX9, and N-WASP. Here, we show at the structural level how a single effector protein can hijack central components of the host's endocytic system for efficient internalization.

PubMed: 39181890
DOI: 10.1038/s41467-024-51681-3

Experimental method

X-RAY DIFFRACTION (3.3 Å)