表面残基69的电荷性质对1型人类免疫缺陷病毒蛋白酶自身加工的调节作用。
Modulation of human immunodeficiency virus type 1 protease autoprocessing by charge properties of surface residue 69.
作者信息
Huang Liangqun, Sayer Jane M, Swinford Marie, Louis John M, Chen Chaoping
机构信息
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523-1870, USA.
出版信息
J Virol. 2009 Aug;83(15):7789-93. doi: 10.1128/JVI.00473-09. Epub 2009 May 20.
Abstract
Mature, fully active human immunodeficiency virus protease (PR) is liberated from the Gag-Pol precursor via regulated autoprocessing. A chimeric protease precursor, glutathione S-transferase-transframe region (TFR)-PR-FLAG, also undergoes N-terminal autocatalytic maturation when it is expressed in Escherichia coli. Mutation of the surface residue H69 to glutamic acid, but not to several neutral or basic amino acids, impedes protease autoprocessing in bacteria and mammalian cells. Only a fraction of mature PR with an H69E mutation (PR(H69E)) folds into active enzymes, and it does so with an apparent Kd (dissociation constant) significantly higher than that of the wild-type protease, corroborating the marked retardation of the in vitro N-terminal autocatalytic processing of TFR-PR(H69E) and suggesting a folding defect in the precursor.
摘要
成熟、具有完全活性的人类免疫缺陷病毒蛋白酶（PR）通过受调控的自身加工过程从Gag-Pol前体中释放出来。一种嵌合蛋白酶前体，即谷胱甘肽S-转移酶-跨框区（TFR）-PR-FLAG，当在大肠杆菌中表达时也会经历N端自催化成熟过程。表面残基H69突变为谷氨酸，但不是突变为几种中性或碱性氨基酸，会阻碍细菌和哺乳动物细胞中的蛋白酶自身加工。只有一小部分具有H69E突变的成熟PR（PR(H69E)）折叠成活性酶，并且其解离常数（Kd）明显高于野生型蛋白酶，这证实了TFR-PR(H69E)体外N端自催化加工的显著延迟，并表明前体存在折叠缺陷。
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