9B85

Cryo-EM structure of human dynactin complex bound to Chlamydia effector Dre1

Summary for 9B85

• Entry DOI: 10.2210/pdb9b85/pdb
• EMDB information: 44333
• Descriptor: Alpha-centractin, ADENOSINE-5'-DIPHOSPHATE, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (12 entities in total)
• Functional Keywords: human dynactin, chlamydia effector, host-pathogen interaction, motor protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 19
• Total formula weight: 767735.67

Authors

Pawar, K.I.,Verba, K.A. (deposition date: 2024-03-28, release date: 2025-04-16)

Primary citation

Sherry, J.,Pawar, K.I.,Dolat, L.,Smith, E.,Chang, I.C.,Pha, K.,Kaake, R.,Swaney, D.L.,Herrera, C.,McMahon, E.,Bastidas, R.J.,Johnson, J.R.,Valdivia, R.H.,Krogan, N.J.,Elwell, C.A.,Verba, K.,Engel, J.N.
The Chlamydia effector Dre1 binds dynactin to reposition host organelles during infection.
Cell Rep, 44:115509-115509, 2025

PubMed Abstract: The 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.

PubMed: 40186871
DOI: 10.1016/j.celrep.2025.115509

Experimental method

ELECTRON MICROSCOPY (3.47 Å)