Structure and mechanism of CRISPR-Cas type IV systems

CRISPR-Cas系统是一种在结构和机制上高度多样化的原核生物适应性免疫系统，可防止移动遗传元件。I类CRISPR-Cas系统具有多亚基效应复合物。我们最近可以证明，即使是密切相关的亚型，即I-F型和I-F变体（I-Fv），在结构和DNA监视机制上也存在很大差异。此外，CRISPR-Cas系统已被认为在非规范过程中发挥作用，例如转录控制、应激反应和致病性发展。其他人和我们可以证明CRISPR适应蛋白Cas1与氧化还原-应激传感和信号双组分系统YedVW相互作用。本提案的目的是对尚不了解的I类CRISPR-Cas系统，如希瓦氏腐菌I- fv型和质粒携带的Aromatoleum aromaticum IV型系统，进行详细的结构、机制和功能理解。此外，我们旨在了解Cas1和YedVW在氧化还原-应激诱导的大肠杆菌应激反应中的相互作用的结构、机制和功能。

CRISPR-Cas systems are structurally and mechanistically highly diverse prokaryotic adaptive immune systems that protect against mobile genetic elements. Class I CRISPR-Cas systems feature multi-subunit effector complexes. We could recently demonstrate that even closely related subtypes, i.e. the type I-F and I-F variant (I-Fv), differ substantially in their structure and DNA surveillance mechanism. Furthermore, CRISPR-Cas systems have been implied to function in non-canonical processes, such as e.g. transcriptional control, stress response and pathogenicity development. Others and we could show that the CRISPR adaptation protein Cas1 interacts with the redox-stress sensing and signaling two-component system YedVW. The aim of this proposal is to produce an en-detail structural, mechanistic and functional understanding of poorly understood class I CRISPR-Cas systems, such as e.g. the Shewanella putrefaciens type I-Fv and the plasmid borne Aromatoleum aromaticum type IV system. Moreover, we aim at a structural, mechanistic and functional understanding of the interaction of Cas1 and YedVW in the redox-stress induced stress response of Escherichia coli.