4bjt
From Proteopedia
Crystal structure of the Rap1 C-terminal domain (Rap1-RCT) in complex with the Rap1 binding module of Rif1 (Rif1-RBM)
Structural highlights
Function[RAP1_YEAST] Essential regulatory protein in yeast whose DNA-binding sites are found at three types of chromosomal elements: promoters, silencers, and telomeres. RAP1 is also involved in the regulation of telomere structure, where its binding sites are found within the terminal poly[C(1-3)A] sequences. The opposite regulatory functions of RAP1 are not intrinsic to its binding sites but, instead, result from interactions with different factors at promoters and silencers. RAP1 associates with SIR3 and SIR4 proteins to form a DNA-binding complex that initiates the repression at the HM loci and telomeres. May also target the binding of RIF1 and RIF2 to silencers and telomeres. Forms with GCR1 a transcriptional activation complex that is required for expression of glycolytic and ribosomal gene. [RIF1_YEAST] Negatively regulates telomere length by preventing telomere elongation or promoting degradation of the telomere ends. Recruited to telomeres by interaction with the C-terminus of RAP1, which binds directly to telomeric repeat DNA. This may create a negative feedback loop in which the addition of new telomere repeats creates binding sites for inhibitors of telomere length extension. May also influence the balance of transcriptional silencing at telomeres and the silent mating type locus HMR, which is mediated by SIR (Silent Information Regulator) proteins including SIR3 and SIR4. RIF1 competes with SIR proteins for binding to the C-terminus of RAP1. In the absence of RIF1, a limiting cellular pool of SIR proteins may preferentially associate with RAP1 at sub-telomeric loci, causing enhanced telomeric silencing and attenuated silencing of the HMR locus.[1] [2] [3] [4] [5] Publication Abstract from PubMedYeast telomeres comprise irregular TG1-3 DNA repeats bound by the general transcription factor Rap1. Rif1 and Rif2, along with Rap1, form the telosome, a protective cap that inhibits telomerase, counteracts SIR-mediated transcriptional silencing, and prevents inadvertent recognition of telomeres as DNA double-strand breaks. We provide a molecular, biochemical, and functional dissection of the protein backbone at the core of the yeast telosome. The X-ray structures of Rif1 and Rif2 bound to the Rap1 C-terminal domain and that of the Rif1 C terminus are presented. Both Rif1 and Rif2 have separable and independent Rap1-binding epitopes, allowing Rap1 binding over large distances (42-110 A). We identify tetramerization (Rif1) and polymerization (Rif2) modules that, in conjunction with the long-range binding, give rise to a higher-order architecture that interlinks Rap1 units. This molecular Velcro relies on Rif1 and Rif2 to recruit and stabilize Rap1 on telomeric arrays and is required for telomere homeostasis in vivo. Rif1 and Rif2 Shape Telomere Function and Architecture through Multivalent Rap1 Interactions.,Shi T, Bunker RD, Mattarocci S, Ribeyre C, Faty M, Gut H, Scrima A, Rass U, Rubin SM, Shore D, Thoma NH Cell. 2013 Jun 6;153(6):1340-53. doi: 10.1016/j.cell.2013.05.007. PMID:23746845[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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