Structure of the Cdt1 C‐terminal domain: Conservation of the winged helix fold in replication licensing factors |
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| Authors: | Bulat I Khayrutdinov Won Jin Bae Young Mi Yun Jie Hye Lee Takashi Tsuyama Jung Joo Kim Eunha Hwang Kyoung‐Seok Ryu Hae‐Kap Cheong Chaejoon Cheong Jung‐Soon Ko Takemi Enomoto P Andrew Karplus Peter Güntert Shusuke Tada Young Ho Jeon Yunje Cho |
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| Institution: | 1. The Magnetic Resonance Team, Korea Basic Science Institute, 804‐1 Yangchung‐Ri, Ochang, Chungbuk 363‐883, South Korea;2. Bulat I. Khayrutdinov, Won Jin Bae, and Young Mi Yun contributed equally to this work.;3. National Creative Research Center for Structural Biology and Department of Life Science, Pohang University of Science and Technology, Hyo‐ja dong, San31, Pohang, KyungBook, South Korea;4. Graduate School of Phamarceutical Sciences, Tohoku University, Aoba‐Ku, Senda, Miyagi 980‐8578, Japan;5. Department of Biochemistry and Biophysics, Oregon State University, Corvallis, Oregon 97330;6. RIKEN Genomic Sciences Center, 1‐7‐22 Suehiro‐cho, Tsurumi, Yokohama 230‐0045, Japan;7. Bio‐analytical Science Program, University of Science and Technology, Kwahakro 113, Yuseong, Daejeon, South Korea |
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| Abstract: | In eukaryotic replication licensing, Cdt1 plays a key role by recruiting the MCM2‐7 complex onto the origin of chromosome. The C‐terminal domain of mouse Cdt1 (mCdt1C), the most conserved region in Cdt1, is essential for licensing and directly interacts with the MCM2‐7 complex. We have determined the structures of mCdt1CS (mCdt1C_small; residues 452 to 557) and mCdt1CL (mCdt1C_large; residues 420 to 557) using X‐ray crystallography and solution NMR spectroscopy, respectively. While the N‐terminal 31 residues of mCdt1CL form a flexible loop with a short helix near the middle, the rest of mCdt1C folds into a winged helix structure. Together with the middle domain of mouse Cdt1 (mCdt1M, residues 172–368), this study reveals that Cdt1 is formed with a tandem repeat of the winged helix domain. The winged helix fold is also conserved in other licensing factors including archaeal ORC and Cdc6, which supports an idea that these replication initiators may have evolved from a common ancestor. Based on the structure of mCdt1C, in conjunction with the biochemical analysis, we propose a binding site for the MCM complex within the mCdt1C. |
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| Keywords: | mouse Cdt1 replication licensing factor winged helix fold mcm binding |
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