Mot1-TBP complex

Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP

Nature. 2011 Jul 6;475(7356):403-7

To reveal how Mot1 specifically disrupts TBP–DNA complexes, we combined crystal and electron microscopy structures of Mot1–TBP from Encephalitozoon cuniculi with biochemical studies. Here we show that Mot1 wraps around TBP and seems to act like a bottle opener: a spring-like array of 16 HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats grips the DNA-distal side of TBP via loop insertions, and the Swi2/Snf2 domain binds to upstream DNA, positioned to weaken the TBP–DNA interaction by DNA translocation. A ‘latch’ subsequently blocks the DNA-binding groove of TBP, acting as a chaperone to prevent DNA re-association and ensure efficient promoter clearance. This work shows how a remodelling enzyme can combine both motor and chaperone activities to achieve functional specificity using a conserved Swi2/Snf2 translocase.

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