5mqi
From Proteopedia
Crystal structure of the N-terminal domain of human Timeless
Structural highlights
FunctionTIM_HUMAN Plays an important role in the control of DNA replication, maintenance of replication fork stability, maintenance of genome stability throughout normal DNA replication and in the regulation of the circadian clock. Involved in the determination of period length and in the DNA damage-dependent phase advancing of the circadian clock. Negatively regulates CLOCK|NPAS2-ARTNL/BMAL1|ARTNL2/BMAL2-induced transactivation of PER1 possibly via translocation of PER1 into the nucleus. Forms a complex with TIPIN and this complex regulates DNA replication processes under both normal and stress conditions, stabilizes replication forks and influences both CHEK1 phosphorylation and the intra-S phase checkpoint in response to genotoxic stress. Timeless promotes TIPIN nuclear localization. Involved in cell survival after DNA damage or replication stress. May be specifically required for the ATR-CHEK1 pathway in the replication checkpoint induced by hydroxyurea or ultraviolet light. May also play an important role in epithelial cell morphogenesis and formation of branching tubules.[1] [2] [3] [4] Publication Abstract from PubMedHuman Timeless is involved in replication fork stabilization, S-phase checkpoint activation and establishment of sister chromatid cohesion. In the cell, Timeless forms a constitutive heterodimeric complex with Tipin. Here we present the 1.85 A crystal structure of a large N-terminal segment of human Timeless, spanning amino acids 1-463, and we show that this region of human Timeless harbours a partial binding site for Tipin. Furthermore, we identify minimal regions of the two proteins that are required for the formation of a stable Timeless-Tipin complex and provide evidence that the Timeless-Tipin interaction is based on a composite binding interface comprising different domains of Timeless. Crystal structure of the N-terminal domain of human Timeless and its interaction with Tipin.,Holzer S, Degliesposti G, Kilkenny ML, Maslen SL, Matak-Vinkovic D, Skehel M, Pellegrini L Nucleic Acids Res. 2017 Feb 25. doi: 10.1093/nar/gkx139. PMID:28334766[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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