RNA polymerase II–TFIIB structure and mechanism of transcription initiation

• Published in: Nature (London) 2009-11, Vol.462 (7271), p.323-330
• Main Authors: Kostrewa, Dirk, Zeller, Mirijam E., Armache, Karim-Jean, Seizl, Martin, Leike, Kristin, Thomm, Michael, Cramer, Patrick
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Bacteria; Bacterial Proteins - chemistry; Biological and medical sciences; Crystalline structure; Deoxyribonucleic acid; DNA; DNA Polymerase II - chemistry; DNA Polymerase II - metabolism; E coli; Enzymes; Fundamental and applied biological sciences. Psychology; Humanities and Social Sciences; Humans; Models, Molecular; Molecular biophysics; Molecular Sequence Data; multidisciplinary; Physiological aspects; Protein Structure, Quaternary; Proteins; RNA polymerases; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Science; Science (multidisciplinary); Sequence Alignment; Structure; Structure in molecular biology; TATA-Box Binding Protein - chemistry; TATA-Box Binding Protein - metabolism; Transcription Factor TFIIB - chemistry; Transcription Factor TFIIB - metabolism; Transcription factors
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature08548

To initiate gene transcription, RNA polymerase II (Pol II) requires the transcription factor IIB (B). Here we present the crystal structure of the complete Pol II–B complex at 4.3 Å resolution, and complementary functional data. The results indicate the mechanism of transcription initiation, including the transition to RNA elongation. Promoter DNA is positioned over the Pol II active centre cleft with the ‘B-core’ domain that binds the wall at the end of the cleft. DNA is then opened with the help of the ‘B-linker’ that binds the Pol II rudder and clamp coiled-coil at the edge of the cleft. The DNA template strand slips into the cleft and is scanned for the transcription start site with the help of the ‘B-reader’ that approaches the active site. Synthesis of the RNA chain and rewinding of upstream DNA displace the B-reader and B-linker, respectively, to trigger B release and elongation complex formation. Gene transcription: new readers start here RNA polymerase II (Pol II) is the central enzyme of gene transcription, making all messenger RNA in eukaryotic cells. Transcription of protein-coding genes is initiated by a complex of Pol II and general transcription factors including TFIIB. Kostrewa et al . have determined the crystal structure of the complete Pol II/TFIIB complex. The structure, together with complementary functional data, suggests a six-step mechanism of transcription initiation, including the transition to RNA elongation triggered when the transcription start site is located. Transcription of eukaryotic protein-coding genes is initiated by RNA polymerase II (Pol II) in a complex with transcription factors including the transcription factor IIB (B). The crystal structure of the complete Pol II–B complex is now presented with complementary functional data. The results shed light on the mechanism of transcription initiation, including the transition to RNA elongation.