Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Structure. 2019 Mar 5;27(3):420-426. doi: 10.1016/j.str.2018.11.011. Epub 2019 Jan 10.
There has been a steadily increasing appreciation of the fact that the relationship between protein sequence and structure is often sufficiently ambiguous to allow a single sequence to adopt alternative, stable folds. Living organisms have been able to utilize such metamorphic proteins in remarkable and unanticipated ways. HIV-1 reverse transcriptase is among the earliest such proteins identified and remains a unique example in which a functional heterodimer contains two, alternatively folded polymerase domains. Structural characterization of the p66 precursor protein combined with NMR spectroscopic and molecular modeling studies have provided insights into the factors underlying the metamorphic transition and the subunit-specific programmed unfolding step required to expose the protease cleavage site within the ribonuclease H domain, supporting the conversion of the p66/p66' precursor into the mature p66/p51 heterodimer.
人们越来越认识到，蛋白质序列和结构之间的关系往往存在足够的模糊性，以至于单个序列可以采用替代的、稳定的折叠方式。生物体已经能够以惊人的、意想不到的方式利用这种变形蛋白。HIV-1 逆转录酶就是最早被发现的这类蛋白之一，它仍然是一个独特的例子，其中功能性异二聚体包含两个折叠方式不同的聚合酶结构域。对 p66 前体蛋白的结构特征进行了描述，并结合 NMR 光谱和分子建模研究，深入了解了变形转换的基础以及在核糖核酸酶 H 结构域内暴露蛋白酶切割位点所需的亚基特异性程序化展开步骤，支持了 p66/p66' 前体转化为成熟的 p66/p51 异二聚体的过程。
