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Structure of nevanimibe-bound tetrameric human ACAT1 期刊论文
NATURE, 2020, 581 (7808) : 339-U214
作者:  Ma, Xiyu;  Claus, Lucas A. N.;  Leslie, Michelle E.;  Tao, Kai;  Wu, Zhiping;  Liu, Jun;  Yu, Xiao;  Li, Bo;  Zhou, Jinggeng;  Savatin, Daniel V.;  Peng, Junmin;  Tyler, Brett M.;  Heese, Antje;  Russinova, Eugenia;  He, Ping;  Shan, Libo
收藏  |  浏览/下载：28/0  |  提交时间：2020/07/03

The structure of human ACAT1 in complex with the inhibitor nevanimibe is resolved by cryo-electron microscopy.


Cholesterol is an essential component of mammalian cell membranes, constituting up to 50% of plasma membrane lipids. By contrast, it accounts for only 5% of lipids in the endoplasmic reticulum (ER)(1). The ER enzyme sterol O-acyltransferase 1 (also named acyl-coenzyme A:cholesterol acyltransferase, ACAT1) transfers a long-chain fatty acid to cholesterol to form cholesteryl esters that coalesce into cytosolic lipid droplets. Under conditions of cholesterol overload, ACAT1 maintains the low cholesterol concentration of the ER and thereby has an essential role in cholesterol homeostasis(2,3). ACAT1 has also been implicated in Alzheimer'  s disease(4), atherosclerosis(5) and cancers(6). Here we report a cryo-electron microscopy structure of human ACAT1 in complex with nevanimibe(7), an inhibitor that is in clinical trials for the treatment of congenital adrenal hyperplasia. The ACAT1 holoenzyme is a tetramer that consists of two homodimers. Each monomer contains nine transmembrane helices (TMs), six of which (TM4-TM9) form a cavity that accommodates nevanimibe and an endogenous acyl-coenzyme A. This cavity also contains a histidine that has previously been identified as essential for catalytic activity(8). Our structural data and biochemical analyses provide a physical model to explain the process of cholesterol esterification, as well as details of the interaction between nevanimibe and ACAT1, which may help to accelerate the development of ACAT1 inhibitors to treat related diseases.


  
Universal quantum logic in hot silicon qubits 期刊论文
NATURE, 2020, 580 (7803) : 355-+
作者:  Li, Jia;  Yang, Xiangdong;  Liu, Yang;  Huang, Bolong;  Wu, Ruixia;  Zhang, Zhengwei;  Zhao, Bei;  Ma, Huifang;  Dang, Weiqi;  Wei, Zheng;  Wang, Kai;  Lin, Zhaoyang;  Yan, Xingxu;  Sun, Mingzi;  Li, Bo;  Pan, Xiaoqing;  Luo, Jun;  Zhang, Guangyu;  Liu, Yuan;  Huang, Yu;  Duan, Xidong;  Duan, Xiangfeng
收藏  |  浏览/下载：40/0  |  提交时间：2020/07/03

Quantum computation requires many qubits that can be coherently controlled and coupled to each other(1). Qubits that are defined using lithographic techniques have been suggested to enable the development of scalable quantum systems because they can be implemented using semiconductor fabrication technology(2-5). However, leading solid-state approaches function only at temperatures below 100 millikelvin, where cooling power is extremely limited, and this severely affects the prospects of practical quantum computation. Recent studies of electron spins in silicon have made progress towards a platform that can be operated at higher temperatures by demonstrating long spin lifetimes(6), gate-based spin readout(7) and coherent single-spin control(8). However, a high-temperature two-qubit logic gate has not yet been demonstrated. Here we show that silicon quantum dots can have sufficient thermal robustness to enable the execution of a universal gate set at temperatures greater than one kelvin. We obtain single-qubit control via electron spin resonance and readout using Pauli spin blockade. In addition, we show individual coherent control of two qubits and measure single-qubit fidelities of up to 99.3 per cent. We demonstrate the tunability of the exchange interaction between the two spins from 0.5 to 18 megahertz and use it to execute coherent two-qubit controlled rotations. The demonstration of '  hot'  and universal quantum logic in a semiconductor platform paves the way for quantum integrated circuits that host both the quantum hardware and its control circuitry on the same chip, providing a scalable approach towards practical quantum information processing.