小柯机器人

美国伊利诺伊大学香槟分校Aleksei Aksimentiev研究组揭示包装噬菌体颗粒的结构和物理特性。2024年3月6日，《自然》杂志在线发表了这项成果。

研究人员报告了通过多分辨率模拟获得的HK97病毒的全原子结构模型，包括其整个39732碱基对的基因组。通过模拟包装马达的作用，基因组被逐渐装入衣壳。然后，通过分辨率不断提高的模拟来完善包装后的噬菌体结构，最终生成了一个包含噬菌体内的水和离子在内的2600万个原子的完整病毒体模型。

DNA包装是通过环状挤压机制进行的，这种机制可产生全局不同的包装基因组构型，并赋予每个病毒粒子以各自的特征。多微秒长的全原子模拟描述了包装基因组对衣壳结构、内部压力、静电以及水、离子和DNA扩散的影响，并揭示了衣壳对基因组的结构印记。这个方法可以推广到其他病毒种类，以获得完整的全原子结构模型，从而有可能在基因组-噬菌体界面发现新的药物靶点。

据了解，一串核苷酸被封闭在蛋白质衣壳中，其中包含了制造功能性病毒粒子（病毒体）的所有必要指令。尽管许多病毒物种的蛋白衣壳结构已经为人所知，但病毒基因组的三维组织结构却大多无法通过实验探究。

附：英文原文

Title: The structure and physical properties of a packaged bacteriophage particle

Author: Coshic, Kush, Maffeo, Christopher, Winogradoff, David, Aksimentiev, Aleksei

Issue&Volume: 2024-03-06

Abstract: A string of nucleotides confined within a protein capsid contains all the instructions necessary to make a functional virus particle, a virion. Although the structure of the protein capsid is known for many virus species1,2, the three-dimensional organization of viral genomes has mostly eluded experimental probes3,4. Here we report all-atom structural models of an HK97 virion5, including its entire 39,732 base pair genome, obtained through multiresolution simulations. Mimicking the action of a packaging motor6, the genome was gradually loaded into the capsid. The structure of the packaged capsid was then refined through simulations of increasing resolution, which produced a 26million atom model of the complete virion, including water and ions confined within the capsid. DNA packaging occurs through a loop extrusion mechanism7 that produces globally different configurations of the packaged genome and gives each viral particle individual traits. Multiple microsecond-long all-atom simulations characterized the effect of the packaged genome on capsid structure, internal pressure, electrostatics and diffusion of water, ions and DNA, and revealed the structural imprints of the capsid onto the genome. Our approach can be generalized to obtain complete all-atom structural models of other virus species, thereby potentially revealing new drug targets at the genome–capsid interface.

DOI: 10.1038/s41586-024-07150-4

Source: https://www.nature.com/articles/s41586-024-07150-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html