| Structural highlights
Function
[CDT1_MOUSE] Cooperates with CDC6 to promote the loading of the mini-chromosome maintenance complex onto chromatin to form the pre-replication complex necessary to initiate DNA replication. Binds DNA in a sequence-, strand-, and conformation-independent manner. Potential oncogene.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Structure of the Cdt1 C-terminal domain: Conservation of the winged helix fold in replication licensing factors.,Khayrutdinov BI, Bae WJ, Yun YM, Lee JH, Tsuyama T, Kim JJ, Hwang E, Ryu KS, Cheong HK, Cheong C, Ko JS, Enomoto T, Karplus PA, Guntert P, Tada S, Jeon YH, Cho Y Protein Sci. 2009 Aug 31. PMID:19722278[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Arentson E, Faloon P, Seo J, Moon E, Studts JM, Fremont DH, Choi K. Oncogenic potential of the DNA replication licensing protein CDT1. Oncogene. 2002 Feb 14;21(8):1150-8. PMID:11850834 doi:http://dx.doi.org/10.1038/sj.onc.1205175
- ↑ Yanagi K, Mizuno T, You Z, Hanaoka F. Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity. J Biol Chem. 2002 Oct 25;277(43):40871-80. Epub 2002 Aug 20. PMID:12192004 doi:http://dx.doi.org/10.1074/jbc.M206202200
- ↑ Sugimoto N, Tatsumi Y, Tsurumi T, Matsukage A, Kiyono T, Nishitani H, Fujita M. Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. J Biol Chem. 2004 May 7;279(19):19691-7. Epub 2004 Mar 1. PMID:14993212 doi:10.1074/jbc.M313175200
- ↑ Khayrutdinov BI, Bae WJ, Yun YM, Lee JH, Tsuyama T, Kim JJ, Hwang E, Ryu KS, Cheong HK, Cheong C, Ko JS, Enomoto T, Karplus PA, Guntert P, Tada S, Jeon YH, Cho Y. Structure of the Cdt1 C-terminal domain: Conservation of the winged helix fold in replication licensing factors. Protein Sci. 2009 Aug 31. PMID:19722278 doi:10.1002/pro.236
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