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科学家设计出融合前的稳定SARS-CoV-2突刺蛋白
作者:小柯机器人 发布时间:2020/7/26 20:01:25

美国德克萨斯大学Jason S. McLellan等研究人员基于结构合作设计出融合前的稳定SARS-CoV-2突刺蛋白。这一研究成果于2020年7月23日在线发表在《科学》上。

研究人员表征了100个结构导向的刺突设计,并鉴定了26个单独的替换残基,这些改变可提高蛋白质产量和稳定性。组合测试鉴定出了HexaPro,这是一种具有六个脯氨酸取代的变体,其表达比其亲本结构高约10倍,并且具有承受热应激,在室温下储存和三个冻融循环的能力。分辨率为3.2Å的HexaPro冷冻电镜结构证实了其保留了融合前突刺构象。
 
高产量生产稳定的融合前刺突蛋白将加速SARS-CoV-2疫苗的开发和血清学诊断。
 
据悉,COVID-19大流行使人们加快了开发疗法和疫苗。这些努力的关键目标是刺突蛋白,但该蛋白是亚稳态的,很难重组产生。
 
附:英文原文

Title: Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

Author: Ching-Lin Hsieh, Jory A. Goldsmith, Jeffrey M. Schaub, Andrea M. DiVenere, Hung-Che Kuo, Kamyab Javanmardi, Kevin C. Le, Daniel Wrapp, Alison G. Lee, Yutong Liu, Chia-Wei Chou, Patrick O. Byrne, Christy K. Hjorth, Nicole V. Johnson, John Ludes-Meyers, Annalee W. Nguyen, Juyeon Park, Nianshuang Wang, Dzifa Amengor, Jason J. Lavinder, Gregory C. Ippolito, Jennifer A. Maynard, Ilya J. Finkelstein, Jason S. McLellan

Issue&Volume: 2020/07/23

Abstract: Abstract The COVID-19 pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. Here, we characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting ~10-fold higher expression than its parental construct and the ability to withstand heat stress, storage at room temperature, and three freeze-thaw cycles. A 3.2 -resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.

DOI: 10.1126/science.abd0826

Source: https://science.sciencemag.org/content/early/2020/07/22/science.abd0826

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037