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Structure of the Cdt1 C‐terminal domain: Conservation of the winged helix fold in replication licensing factors
Author(s) -
Khayrutdinov Bulat I.,
Bae Won Jin,
Yun Young Mi,
Lee Jie Hye,
Tsuyama Takashi,
Kim Jung Joo,
Hwang Eunha,
Ryu KyoungSeok,
Cheong HaeKap,
Cheong Chaejoon,
Ko JungSoon,
Enomoto Takemi,
Karplus P. Andrew,
Güntert Peter,
Tada Shusuke,
Jeon Young Ho,
Cho Yunje
Publication year - 2009
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.236
Subject(s) - dna replication factor cdt1 , origin recognition complex , biology , protein secondary structure , dna replication , chemistry , genetics , dna , control of chromosome duplication , eukaryotic dna replication , biochemistry
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.