A nucleotide-sensing endonuclease from the Gabija bacterial defense system.
A nucleotide-sensing endonuclease from the Gabija bacterial defense system.
复制标题
来自 Gabija 细菌防御系统的核苷酸感应核酸内切酶。
DOI：
10.1093/nar/gkab277
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发表时间：
2021-05-21
影响因子：
14.9
通讯作者：
Zhu B
中科院分区：
文献类型：
--
作者：
Cheng R;Huang F;Wu H;Lu X;Yan Y;Yu B;Wang X;Zhu B
细菌和噬菌体之间的军备竞赛导致了精致的细菌防御系统的发展，包括许多与众所周知的限制性修饰和CRISPR/CAS系统不同的未表征的系统。在这里，我们报告了新预测的Gabija系统的GAJA蛋白的功能分析。 GAJA蛋白被揭示为一种序列特异性DNA核核酸内切酶，因为其活性严格受核苷酸浓度的调节。在生理浓度下的NTP和DNTP可以完全抑制GAJA的稳健DNA裂解活性。有趣的是，核苷酸抑制是由ATPase样结构域介导的，ATPase样结构域通常水解ATP以刺激与其他核酸酶相关的DNA裂解。这些特征表明了Gabija防御的机制，在正常情况下，内切核酸酶活性被抑制，而在复制和转录入侵噬菌体后，NTP和DNTP的耗竭会激活它。这项工作突出了一种简洁的策略，它利用DNA划痕内切核酸酶通过核苷酸调节来抗噬菌体。
The arms race between bacteria and phages has led to the development of exquisite bacterial defense systems including a number of uncharacterized systems distinct from the well-known restriction-modification and CRISPR/Cas systems. Here, we report functional analyses of the GajA protein from the newly predicted Gabija system. The GajA protein is revealed as a sequence-specific DNA nicking endonuclease unique in that its activity is strictly regulated by nucleotide concentration. NTP and dNTP at physiological concentrations can fully inhibit the robust DNA cleavage activity of GajA. Interestingly, the nucleotide inhibition is mediated by an ATPase-like domain, which usually hydrolyzes ATP to stimulate the DNA cleavage when associated with other nucleases. These features suggest a mechanism of the Gabija defense in which an endonuclease activity is suppressed under normal conditions, while it is activated by the depletion of NTP and dNTP upon the replication and transcription of invading phages. This work highlights a concise strategy to utilize a DNA nicking endonuclease for phage resistance via nucleotide regulation.
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影响因子：
5.6
作者：
HIGASHITANI, A;GREENSTEIN, D;HORIUCHI, K
通讯作者：
HORIUCHI, K
DOI：
10.1126/science.aba0372
发表时间：
2020-08-28
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gao L;Altae-Tran H;Böhning F;Makarova KS;Segel M;Schmid-Burgk JL;Koob J;Wolf YI;Koonin EV;Zhang F
通讯作者：
Zhang F
影响因子：
3.6
作者：
Anjem A;Varghese S;Imlay JA
通讯作者：
Imlay JA
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
14.9
作者：
Gordeeva, Julia;Morozova, Natalya;Severinov, Konstantin
通讯作者：
Severinov, Konstantin