- EMDB-9400: Cryo-EM structure of Mcm2-7 double hexamer on dsDNA -
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基本情報
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データベース: EMDB / ID: EMD-9400
タイトル
Cryo-EM structure of Mcm2-7 double hexamer on dsDNA
マップデータ
Mcm2-7 double hexamer on dsDNA
試料
複合体: Mcm double hexamer bound to double-stranded DNA
複合体: Mcm double hexamer
タンパク質・ペプチド: DNA replication licensing factor MCM2
タンパク質・ペプチド: DNA replication licensing factor MCM3
タンパク質・ペプチド: DNA replication licensing factor MCM4
タンパク質・ペプチド: DNA replication licensing factor MCM5
タンパク質・ペプチド: DNA replication licensing factor MCM6
タンパク質・ペプチド: DNA replication licensing factor MCM7
複合体: synthetic double-stranded DNA
DNA: DNA (60-mer), strand 1
DNA: DNA (60-mer), strand 2
リガンド: ADENOSINE-5'-DIPHOSPHATE
キーワード
complex / DNA replication / HYDROLASE-DNA complex
機能・相同性
機能・相同性情報
MCM core complex / Assembly of the pre-replicative complex / Switching of origins to a post-replicative state / MCM complex binding / nuclear DNA replication / premeiotic DNA replication / replication fork protection complex / pre-replicative complex assembly involved in nuclear cell cycle DNA replication / mitotic DNA replication / Activation of the pre-replicative complex ...MCM core complex / Assembly of the pre-replicative complex / Switching of origins to a post-replicative state / MCM complex binding / nuclear DNA replication / premeiotic DNA replication / replication fork protection complex / pre-replicative complex assembly involved in nuclear cell cycle DNA replication / mitotic DNA replication / Activation of the pre-replicative complex / CMG complex / nuclear pre-replicative complex / Activation of ATR in response to replication stress / DNA replication preinitiation complex / MCM complex / double-strand break repair via break-induced replication / mitotic DNA replication initiation / single-stranded DNA helicase activity / regulation of DNA-templated DNA replication initiation / silent mating-type cassette heterochromatin formation / DNA strand elongation involved in DNA replication / nuclear replication fork / DNA replication origin binding / DNA replication initiation / subtelomeric heterochromatin formation / DNA helicase activity / transcription elongation by RNA polymerase II / helicase activity / heterochromatin formation / single-stranded DNA binding / DNA helicase / chromosome, telomeric region / DNA replication / DNA damage response / chromatin binding / ATP hydrolysis activity / zinc ion binding / nucleoplasm / ATP binding / nucleus / cytoplasm 類似検索 - 分子機能
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM111472
米国
引用
ジャーナル: Proc Natl Acad Sci U S A / 年: 2017 タイトル: Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a lagging-strand DNA extrusion model. 著者: Yasunori Noguchi / Zuanning Yuan / Lin Bai / Sarah Schneider / Gongpu Zhao / Bruce Stillman / Christian Speck / Huilin Li / 要旨: During replication initiation, the core component of the helicase-the Mcm2-7 hexamer-is loaded on origin DNA as a double hexamer (DH). The two ring-shaped hexamers are staggered, leading to a kinked ...During replication initiation, the core component of the helicase-the Mcm2-7 hexamer-is loaded on origin DNA as a double hexamer (DH). The two ring-shaped hexamers are staggered, leading to a kinked axial channel. How the origin DNA interacts with the axial channel is not understood, but the interaction could provide key insights into Mcm2-7 function and regulation. Here, we report the cryo-EM structure of the Mcm2-7 DH on dsDNA and show that the DNA is zigzagged inside the central channel. Several of the Mcm subunit DNA-binding loops, such as the oligosaccharide-oligonucleotide loops, helix 2 insertion loops, and presensor 1 (PS1) loops, are well defined, and many of them interact extensively with the DNA. The PS1 loops of Mcm 3, 4, 6, and 7, but not 2 and 5, engage the lagging strand with an approximate step size of one base per subunit. Staggered coupling of the two opposing hexamers positions the DNA right in front of the two Mcm2-Mcm5 gates, with each strand being pressed against one gate. The architecture suggests that lagging-strand extrusion initiates in the middle of the DH that is composed of the zinc finger domains of both hexamers. To convert the Mcm2-7 DH structure into the Mcm2-7 hexamer structure found in the active helicase, the N-tier ring of the Mcm2-7 hexamer in the DH-dsDNA needs to tilt and shift laterally. We suggest that these N-tier ring movements cause the DNA strand separation and lagging-strand extrusion.