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Structure paper

TitleThe Chlamydia effector Dre1 binds dynactin to reposition host organelles during infection.
Journal, issue, pagesCell Rep, Vol. 44, Issue 4, Page 115509, Year 2025
Publish dateApr 3, 2025
AuthorsJessica Sherry / Komal Ishwar Pawar / Lee Dolat / Erin Smith / I-Chang Chang / Khavong Pha / Robyn Kaake / Danielle L Swaney / Clara Herrera / Eleanor McMahon / Robert J Bastidas / Jeffrey R Johnson / Raphael H Valdivia / Nevan J Krogan / Cherilyn A Elwell / Kliment Verba / Joanne N Engel /
PubMed AbstractThe obligate intracellular pathogen Chlamydia trachomatis replicates in a specialized membrane-bound compartment where it repositions host organelles during infection to acquire nutrients and evade ...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.
External linksCell Rep / PubMed:40186871 / PubMed Central
MethodsEM (single particle)
Resolution3.47 - 3.49 Å
Structure data

44306

9b7j

EMDB-44306, PDB-9b7j:
Cryo-EM structure of human dynactin complex bound to Chlamydia effector Dre1
Method: EM (single particle) / Resolution: 3.49 Å

44333

9b85

EMDB-44333, PDB-9b85:
Cryo-EM structure of human dynactin complex bound to Chlamydia effector Dre1
Method: EM (single particle) / Resolution: 3.47 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

ChemComp-ZN:
Unknown entry

Source
  • homo sapiens (human)
KeywordsMOTOR PROTEIN / Human dynactin / Chlamydia effector / host-pathogen interaction

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