1,721,255 research outputs found
AlphaFold2 and the future of structural biology
Full text linkAlphaFold2 is a machine-learning algorithm for protein structure prediction that has now been used to obtain hundreds of thousands of protein models. The resulting resource is marvelous and will serve the community in many ways. Here I discuss the implications of this breakthrough achievement, which changes the way we do structural biology
Organization and regulation of gene transcription.
No full textThe regulated transcription of genes determines cell identity and function. Recent structural studies have elucidated mechanisms that govern the regulation of transcription by RNA polymerases during the initiation and elongation phases. Microscopy studies have revealed that transcription involves the condensation of factors in the cell nucleus. A model is emerging for the transcription of protein-coding genes in which distinct transient condensates form at gene promoters and in gene bodies to concentrate the factors required for transcription initiation and elongation, respectively. The transcribing enzyme RNA polymerase II may shuttle between these condensates in a phosphorylation-dependent manner. Molecular principles are being defined that rationalize transcriptional organization and regulation, and that will guide future investigations
Multisubunit RNA polymerases
No full textTranscription of the genetic information in all cells is carried out by multisubunit RNA polymerases (RNAPs). Comparison of the crystal structures of a bacterial and a eukaryotic RNAP reveals a conserved core that comprises the active site and a multifunctional clamp. Together with a further structure of eukaryotic RNAP bound to DNA and RNA, these results elucidate many aspects of the transcription mechanism, including initiation, elongation, nucleotide addition, processivity and proofreading
Towards molecular systems biology of gene transcription and regulation
Full text linkTen years after the determination of the RNA polymerase 11 structure, the basic mechanism of mRNA synthesis during gene transcription is known. In the future, the initiation and regulation of transcription must be studied with a combination of structural biology, biochemistry, functional genomics, and computational methods. In this article, the efforts of our laboratory to move from an integrated structural biology of gene transcription towards molecular systems biology of gene regulation are reviewed
Structure and Function of RNA Polymerase II
No full textThis chapter discusses the structure and function of RNA polymerase II. High-resolution structural studies of polymerase II (Pol II) by x-ray crystallography required large amounts of pure protein that cannot be obtained by over-expression because of the complexity of the enzyme. The described structural studies of yeast Pol II are directly relevant to Pol II enzymes in higher organisms, because Pol II subunits are very well conserved in sequence and function. After successful RNA chain elongation, transcription terminates and Pol II dissociates from the template. Some of the steps during the transcription cycle can be carried out by Pol II alone. Pol II can maintain an open transcription bubble, translocate along the template DNA, synthesize RNA from the template, and proofread the nascent RNA. However, for all other steps during the transcription cycle, Pol II requires additional proteins. The chapter presents backbone models of the complete initiation-competent Pol II, including the Rpb4/7 complex and the complete Pol II with bound elongation factor transcription factor IIS (TFIIS). The structures, together with many functional studies, have given many insights into the mechanism of mRNA transcription. Structural and functional studies of bacterial RNA polymerase allow for interesting comparisons and evolutionary considerations. The Pol II structures now guide mutagenesis experiments aimed at a dissection of the transcription mechanism
RNA polymerase II structure: From core to functional complexes.
No full textNew structural studies of RNA polymerase II (Pol II) complexes mark the beginning of a detailed mechanistic analysis of the eukaryotic mRNA transcription cycle. Crystallographic models of the complete Pol II, together with new biochemical and electron microscopic data, give insights into transcription initiation. The first X-ray analysis of a Pol II complex with a transcription factor, the elongation factor TFIIS, supports the idea that the polymerase has a ‘tunable’ active site that switches between mRNA synthesis and cleavage. The new studies also show that domains of transcription factors can enter polymerase openings, to modulate function during transcription
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