9b85
Cryo-EM structure of human dynactin complex bound to Chlamydia effector Dre1
Structural highlights
FunctionACTZ_HUMAN Part of the ACTR1A/ACTB filament around which the dynactin complex is built. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules.[UniProtKB:F2Z5G5] Publication Abstract from PubMedThe obligate intracellular pathogen Chlamydia trachomatis replicates in a specialized membrane-bound compartment where it repositions host organelles during infection to acquire nutrients and evade host surveillance. We describe a bacterial effector, Dre1, that binds specifically to dynactin associated with host microtubule organizing centers without globally impeding dynactin function. Dre1 is required to reposition the centrosome, mitotic spindle, Golgi apparatus, and primary cilia around the inclusion and contributes to pathogen fitness in cell-based and mouse models of infection. We utilized Dre1 to affinity purify the megadalton dynactin protein complex and determined the first cryoelectron microscopy (cryo-EM) structure of human dynactin. Our results suggest that Dre1 binds to the pointed end of dynactin and uncovers the first bacterial effector that modulates dynactin function. Our work highlights how a pathogen employs a single effector to evoke targeted, large-scale changes in host cell organization that facilitate pathogen growth without inhibiting host viability. The Chlamydia effector Dre1 binds dynactin to reposition host organelles during infection.,Sherry J, Pawar KI, Dolat L, Smith E, Chang IC, Pha K, Kaake R, Swaney DL, Herrera C, McMahon E, Bastidas RJ, Johnson JR, Valdivia RH, Krogan NJ, Elwell CA, Verba K, Engel JN Cell Rep. 2025 Apr 3;44(4):115509. doi: 10.1016/j.celrep.2025.115509. PMID:40186871[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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