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Structural basis of DNA targeting by a transposon-encoded CRISPR-Cas system 期刊论文
NATURE, 2020, 577 (7789) : 271-+
作者:  Halpin-Healy, Tyler S.;  Klompe, Sanne E.;  Sternberg, Samuel H.;  Fernandez, Israel S.
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/03

Bacteria use adaptive immune systems encoded by CRISPR and Cas genes to maintain genomic integrity when challenged by pathogens and mobile genetic elements(1-3). Type I CRISPR-Cas systems typically target foreign DNA for degradation via joint action of the ribonucleoprotein complex Cascade and the helicase-nuclease Cas3(4,5), but nuclease-deficient type I systems lacking Cas3 have been repurposed for RNA-guided transposition by bacterial Tn7-like transposons(6,7). How CRISPR- and transposon-associated machineries collaborate during DNA targeting and insertion remains unknown. Here we describe structures of a TniQ-Cascade complex encoded by the Vibrio cholerae Tn6677 transposon using cryo-electron microscopy, revealing the mechanistic basis of this functional coupling. The cryo-electron microscopy maps enabled de novo modelling and refinement of the transposition protein TniQ, which binds to the Cascade complex as a dimer in a head-to-tail configuration, at the interface formed by Cas6 and Cas7 near the 3'  end of the CRISPR RNA (crRNA). The natural Cas8-Cas5 fusion protein binds the 5'  crRNA handle and contacts the TniQ dimer via a flexible insertion domain. A target DNA-bound structure reveals critical interactions necessary for protospacer-adjacent motif recognition and R-loop formation. This work lays the foundation for a structural understanding of how DNA targeting by TniQ-Cascade leads to downstream recruitment of additional transposase proteins, and will guide protein engineering efforts to leverage this system for programmable DNA insertions in genome-engineering applications.


  
Fast two-qubit logic with holes in germanium 期刊论文
NATURE, 2020, 577 (7791) : 487-+
作者:  Halpin-Healy, Tyler S.;  Klompe, Sanne E.;  Sternberg, Samuel H.;  Fernandez, Israel S.
收藏  |  浏览/下载:28/0  |  提交时间:2020/07/03

Universal quantum information processing requires the execution of single-qubit and two-qubit logic. Across all qubit realizations(1), spin qubits in quantum dots have great promise to become the central building block for quantum computation(2). Excellent quantum dot control can be achieved in gallium arsenide(3-5), and high-fidelity qubit rotations and two-qubit logic have been demonstrated in silicon(6-9), but universal quantum logic implemented with local control has yet to be demonstrated. Here we make this step by combining all of these desirable aspects using hole quantum dots in germanium. Good control over tunnel coupling and detuning is obtained by exploiting quantum wells with very low disorder, enabling operation at the charge symmetry point for increased qubit performance. Spin-orbit coupling obviates the need for microscopic elements close to each qubit and enables rapid qubit control with driving frequencies exceeding 100 MHz. We demonstrate a fast universal quantum gate set composed of single-qubit gates with a fidelity of 99.3 per cent and a gate time of 20 nanoseconds, and two-qubit logic operations executed within 75 nanoseconds. Planar germanium has thus matured within a year from a material that can host quantum dots to a platform enabling two-qubit logic, positioning itself as an excellent material for use in quantum information applications.


Spin qubits based on hole states in strained germanium could offer the most scalable platform for quantum computation.