3vp8 | pdb_00003vp8
Crystal structure of the N-terminal domain of the yeast general corepressor Tup1p
Structural highlights
Function[TUP1_YEAST] Acts as component of the CYC8-TUP1 corepressor complex which is involved in the repression of many genes in a wide variety of physiological processes including heme-regulated and catabolite repressed genes. May also be involved in the derepression of at least some target genes. The complex is recruited to target genes by interaction with DNA-bound transcriptional repressors, like MATALPHA2, MIG1, RFX1 and SKO1. The complex recruits histone deacetylases to produce a repressive chromatin structure, interacts with hypoacetylated N-terminal tails of histones H3 and H4 that have been programmed for repression by the action of histone deacetylases and interferes directly with the transcriptional machinery by associating with the RNA polymerase II mediator complex.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedThe yeast Cyc8p-Tup1p protein complex is a general transcriptional corepressor of genes involved in many different physiological processes. Herein, we present the crystal structure of the Tup1p N-terminal domain (residues 1-92), essential for Tup1p self-assembly and interaction with Cyc8p. This domain tetramerizes to form a novel antiparallel four-helix bundle. Coiled coil interactions near the helical ends hold each dimer together, whereas interdimeric association involves only two sets of two residues located toward the chain centers. A mutagenesis study confirmed that the nonpolar residues responsible for the association of the protomers as dimers are also required for transcriptional repression. An additional structural study demonstrated that the domain containing an Leu(62) --> Arg mutation that had been shown not to bind Cyc8p exhibits an altered structure, distinct from the wild type. This altered structure explains why the mutant cannot bind Cyc8p. The data presented herein highlight the importance of the architecture of the Tup1p N-terminal domain for self-association. Crystal structure of the N-terminal domain of the yeast general corepressor Tup1p and its functional implications.,Matsumura H, Kusaka N, Nakamura T, Tanaka N, Sagegami K, Uegaki K, Inoue T, Mukai Y J Biol Chem. 2012 Aug 3;287(32):26528-38. Epub 2012 Jun 15. PMID:22707714[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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