3OC3

Crystal structure of the Mot1 N-terminal domain in complex with TBP

Summary for 3OC3

• Entry DOI: 10.2210/pdb3oc3/pdb
• Related: 3OCI
• Descriptor: HELICASE MOT1, TRANSCRIPTION INITIATION FACTOR TFIID (TFIID-1), 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (4 entities in total)
• Functional Keywords: transcription, regulation of transcription, hydrolase-transcription complex, hydrolase/transcription
• Biological source: Encephalitozoon cuniculi (Microsporidian parasite); More
• Total number of polymer chains: 4
• Total formula weight: 233358.34

Authors

Wollmann, P.,Cui, S.,Viswanathan, R.,Berninghausen, O.,Wells, M.N.,Moldt, M.,Witte, G.,Butryn, A.,Wendler, P.,Beckmann, R.,Auble, D.T.,Hopfner, K.-P. (deposition date: 2010-08-09, release date: 2011-07-13, Last modification date: 2024-03-20)

Primary citation

Wollmann, P.,Cui, S.,Viswanathan, R.,Berninghausen, O.,Wells, M.N.,Moldt, M.,Witte, G.,Butryn, A.,Wendler, P.,Beckmann, R.,Auble, D.T.,Hopfner, K.P.
Structure and mechanism of the Swi2/Snf2 remodeller Mot1 in complex with its substrate TBP.
Nature, 475:403-407, 2011

PubMed Abstract: Swi2/Snf2-type ATPases regulate genome-associated processes such as transcription, replication and repair by catalysing the disruption, assembly or remodelling of nucleosomes or other protein-DNA complexes. It has been suggested that ATP-driven motor activity along DNA disrupts target protein-DNA interactions in the remodelling reaction. However, the complex and highly specific remodelling reactions are poorly understood, mostly because of a lack of high-resolution structural information about how remodellers bind to their substrate proteins. Mot1 (modifier of transcription 1 in Saccharomyces cerevisiae, denoted BTAF1 in humans) is a Swi2/Snf2 enzyme that specifically displaces the TATA box binding protein (TBP) from the promoter DNA and regulates transcription globally by generating a highly dynamic TBP pool in the cell. As a Swi2/Snf2 enzyme that functions as a single polypeptide and interacts with a relatively simple substrate, Mot1 offers an ideal system from which to gain a better understanding of this important enzyme family. 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.

PubMed: 21734658
DOI: 10.1038/nature10215

Experimental method

X-RAY DIFFRACTION (3.1 Å)