7uik | pdb_00007uik
Mediator-PIC Early (Tail A + Upstream DNA & Activator)
Structural highlights
FunctionMED15_YEAST Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. It has an important role in the negative regulation of Ty transcription.[1] [2] [3] Publication Abstract from PubMedMost eukaryotic promoter regions are divergently transcribed. As the RNA polymerase II pre-initiation complex (PIC) is intrinsically asymmetric and responsible for transcription in a single direction, it is unknown how divergent transcription arises. Here, the Saccharomyces cerevisiae Mediator complexed with a PIC (Med-PIC) was assembled on a divergent promoter and analyzed by cryoelectron microscopy. The structure reveals two distinct Med-PICs forming a dimer through the Mediator tail module, induced by a homodimeric activator protein localized near the dimerization interface. The tail dimer is associated with approximately 80-bp upstream DNA, such that two flanking core promoter regions are positioned and oriented in a suitable form for PIC assembly in opposite directions. Also, cryoelectron tomography visualized the progress of the PIC assembly on the two core promoter regions, providing direct evidence for the role of the Med-PIC dimer in divergent transcription. Structural basis of a transcription pre-initiation complex on a divergent promoter.,Gorbea Colon JJ, Palao L 3rd, Chen SF, Kim HJ, Snyder L, Chang YW, Tsai KL, Murakami K Mol Cell. 2023 Jan 26:S1097-2765(23)00031-X. doi: 10.1016/j.molcel.2023.01.011. PMID:36731470[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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