Publication Date:
2011-07-08
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276066/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276066/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wollmann, Petra -- Cui, Sheng -- Viswanathan, Ramya -- Berninghausen, Otto -- Wells, Melissa N -- Moldt, Manuela -- Witte, Gregor -- Butryn, Agata -- Wendler, Petra -- Beckmann, Roland -- Auble, David T -- Hopfner, Karl-Peter -- GM55763/GM/NIGMS NIH HHS/ -- R01 GM055763/GM/NIGMS NIH HHS/ -- R01 GM055763-13/GM/NIGMS NIH HHS/ -- England -- Nature. 2011 Jul 6;475(7356):403-7. doi: 10.1038/nature10215.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Ludwig-Maximilians University, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21734658" target="_blank"〉PubMed〈/a〉
Keywords:
Binding Sites
;
Crystallization
;
Crystallography, X-Ray
;
DNA/chemistry/genetics/metabolism/ultrastructure
;
Encephalitozoon cuniculi/*chemistry
;
Fungal Proteins/*chemistry/*metabolism/ultrastructure
;
Microscopy, Electron
;
Models, Biological
;
Models, Molecular
;
Promoter Regions, Genetic/genetics
;
Protein Conformation
;
Protein Structure, Tertiary
;
Structure-Activity Relationship
;
Substrate Specificity
;
TATA-Box Binding Protein/*chemistry/*metabolism/ultrastructure
;
Transcription Factor TFIIB/chemistry/metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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