Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.
Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.
复制标题
DOI：
10.1093/nar/gkad971
复制
发表时间：
2023-12-11
影响因子：
14.9
通讯作者：
Stivers, James T.
中科院分区：
文献类型：
--
作者：
Orris, Benjamin;Sung, Min Woo;Bhat, Shridhar;Xu, Yingrong;Huynh, Kevin W.;Han, Seungil;Johnson, Darren C.;Bosbach, Benedikt;Shields, David J.;Stivers, James T.
含有脱氧核苷三磷酸水解酶1(SAMHD1)的四聚体SAM和HD结构域的dNTPase活性在细胞dNTP调控中起着关键作用。SAMHD1还与停滞的DNA复制叉、DNA修复焦点、单链RNA和端粒有关。上述功能需要SAMHD1与核酸结合，这可能受其寡聚体状态的调节。在这里，我们在冷冻-EM和生化研究中确定，每个SAMHD1单体的鸟嘌呤特异性A1激活位点被用于靶向单链(Ss)DNA和RNA中的鸟嘌呤核苷酸。值得注意的是，含有一个鸟嘌呤碱基的核酸链诱导二聚体SAMHD1，而核苷酸间距为∼20的两个或多个鸟嘌呤诱导四聚体形式。单链RNA结合的四聚体SAMHD1的冷冻EM结构显示了单链RNA是如何连接两个SAMHD1二聚体并稳定结构的。这个与单链RNA结合的四聚体在dNTPase和RNase活性方面是无效的。
The dNTPase activity of tetrameric SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) plays a critical role in cellular dNTP regulation. SAMHD1 also associates with stalled DNA replication forks, DNA repair foci, ssRNA and telomeres. The above functions require nucleic acid binding by SAMHD1, which may be modulated by its oligomeric state. Here we establish in cryo-EM and biochemical studies that the guanine-specific A1 activator site of each SAMHD1 monomer is used to target the enzyme to guanine nucleotides within single-stranded (ss) DNA and RNA. Remarkably, nucleic acid strands containing a single guanine base induce dimeric SAMHD1, while two or more guanines with ∼20 nucleotide spacing induce a tetrameric form. A cryo-EM structure of ssRNA-bound tetrameric SAMHD1 shows how ssRNA strands bridge two SAMHD1 dimers and stabilize the structure. This ssRNA-bound tetramer is inactive with respect to dNTPase and RNase activity.
登录
查看更多内容
影响因子：
14.9
作者：
Perez-Riverol Y;Bai J;Bandla C;García-Seisdedos D;Hewapathirana S;Kamatchinathan S;Kundu DJ;Prakash A;Frericks-Zipper A;Eisenacher M;Walzer M;Wang S;Brazma A;Vizcaíno JA
通讯作者：
Vizcaíno JA
影响因子：
3
作者：
Punjani, Ali;Fleet, David J.
通讯作者：
Fleet, David J.
影响因子：
48
作者：
Punjani, Ali;Rubinstein, John L.;Brubaker, Marcus A.
通讯作者：
Brubaker, Marcus A.
影响因子：
16.8
作者：
Ji, Xiaoyun;Wu, Ying;Yan, Junpeng;Mehrens, Jennifer;Yang, Haitao;DeLucia, Maria;Hao, Caili;Gronenborn, Angela M.;Skowronski, Jacek;Ahn, Jinwoo;Xiong, Yong
通讯作者：
Xiong, Yong
影响因子：
14.9
作者：
Akimova E;Gassner FJ;Schubert M;Rebhandl S;Arzt C;Rauscher S;Tober V;Zaborsky N;Greil R;Geisberger R
通讯作者：
Geisberger R