双链DNA病毒,如疱疹病毒和细菌噬菌体,在感染过程中向细胞内注入其遗传物质,这一病毒基因组的侵入过程由称为门户蛋白(portal protein)的DNA通道介导。2008年2月15日《分子细胞》(Molecular Cell)的封面文章表明,门户蛋白通过构象变化促使噬菌体的成熟和侵入。
噬菌体的生长和繁殖包括吸附、侵入、增殖、成熟和释放多个过程,门户蛋白是噬菌体P22衣壳蛋白的重要成分,以往研究表明它构成物质出入蛋白质衣壳的门户,同时可以连接末端酶和尾丝辅助因子等,在噬菌体的成熟和侵入过程中起重要作用。
来自美国华盛顿大学和纽约州立大学的研究人员用低温电镜技术对处于原衣壳阶段和成熟阶段的噬菌体P22门户蛋白的结构进行研究,发现在该病毒成熟的过程中,门户蛋白的构象发生了很大变化,其构象变化与其功能密切相关。
该研究指出,门户蛋白在原衣壳阶段和成熟阶段以两种不同的构象存在,构象间转变由尾丝因子gp4诱导。当DNA包装过程完成时,gp4与末端酶竞争结合门户蛋白并寡聚化,致使末端酶脱离,门户蛋白的构象同时发生巨大变化,转变为成熟阶段构象,在DNA通道的上方形成圆顶状结构域,该结构域能够夹住通道内的线状DNA双链,并且诱导病毒粒子内的侵入蛋白聚集结合于门户蛋白顶部,其富含精氨酸的片段也于顶部形成高正电的表面以结合酸性的DNA,从而为噬菌体基因组的新一轮侵入做好准备。(科学网 穆宏平/编译)
生物谷推荐原始出处
(Molecular Cell),Vol 29, 376-383, 15 February 2008,Hongjin Zheng, Tamir Gonen
A Conformational Switch in Bacteriophage P22 Portal Protein Primes Genome Injection4
Hongjin Zheng, Adam S. Olia, Melissa Gonen, Simeon Andrews, Gino Cingolani,, and Tamir Gonen1,4
Summary
Double-stranded DNA (dsDNA) viruses such as herpesviruses and bacteriophages infect by delivering their genetic material into cells, a task mediated by a DNA channel called “portal protein.” We have used electron cryomicroscopy to determine the structure of bacteriophage P22 portal protein in both the procapsid and mature capsid conformations. We find that, just as the viral capsid undergoes major conformational changes during virus maturation, the portal protein switches conformation from a procapsid to a mature phage state upon binding of gp4, the factor that initiates tail assembly. This dramatic conformational change traverses the entire length of the DNA channel, from the outside of the virus to the inner shell, and erects a large dome domain directly above the DNA channel that binds dsDNA inside the capsid. We hypothesize that this conformational change primes dsDNA for injection and directly couples completion of virus morphogenesis to a new cycle of infection. |