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Home > How pathogens hijack dynein/dynactin
Andrew Carterss

Andrew Carter

How pathogens hijack dynein/dynactin

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The dynein/dynactin complex is a key microtubule motor that is hijacked by all major classes of viruses.  There are also increasing examples of it being co-opted by intracellular bacterial pathogens.  The different hijacking strategies give unique insights into the pathogen life cycle and can help uncover novel insights into dynein’s cellular roles.

Although several examples of pathogen–motor interactions have been identified, the structural basis of these processes remains poorly understood. Current AlphaFold predictions are typically of low confidence and therefore the goal of this project is to use cryo-electron microscopy (cryoEM) to determine the structural principles underlying motor hijacking. The aim will be to use this information, together with biochemical and cellular assays, to search for novel pathogen effectors which target the dynein transport machinery.

References

The cytoplasmic dynein transport machinery and its many cargoes
Reck-Peterson SL, Redwine WB, Vale RD, Carter AP
Nature Reviews Molecular Cell Biology 19(6): 382-398 (2018)
 
Molecular mechanism of dynein-dynactin complex assembly by LIS1.
Singh K, Lau CK, Manigrasso G, Gama JB, Gassmann R, Carter AP
Science 383(6690): eadk8544 (2024)
 
The intracellular bacterium Orientia tsutsugamushi uses the autotransporter ScaC to activate BICD adaptors for dynein-based motility
Manigrasso G, Saharat K, Chaichana P, Kullapanich C, Atwal S, Boulanger J, Morgan TE, Kramer H, Salje J, Carter AP
Nature Communications 16(1): (2025)
 
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 Reports 44(4): 115509 (2025)

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