Structural Basis for Importin-α Binding of the Human Immunodeficiency Virus Tat

被引:21
作者
Smith, K. M. [1 ]
Himiari, Z. [1 ]
Tsimbalyuk, S. [1 ]
Forwood, J. K. [1 ]
机构
[1] Charles Sturt Univ, Sch Biomed Sci, Wagga Wagga, NSW 2678, Australia
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
NUCLEAR-LOCALIZATION SIGNAL; CRYSTAL-STRUCTURE; PROTEIN; PDBSUM; RECOGNITION; DELIVERY; DOMAIN; DNA; CRYSTALLIZATION; MONOPARTITE;
D O I
10.1038/s41598-017-01853-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
HIV-1 has caused 35 million deaths globally, and approximately the same number is currently living with HIV-1. The trans-activator of transcription (Tat) protein of HIV-1 plays an important regulatory function in the virus life cycle, responsible for regulating the reverse transcription of the viral genome RNA. Tat is found in the nucleus of infected cells, but can also invade uninfected neighbouring cells. Regions within Tat responsible for these cellular localisations are overlapping and include a nuclear localisation signal (NLS) spanning (48)GRKKRR, and a cell penetrating peptide (CPP) signal spanning (48)GRKKRRQRRRAPQN. However, the mechanism by which this NLS/CPP region mediates interaction with the nuclear import receptors remains to be resolved structurally. Here, we establish that the HIV-1 Tat: NLS/CPP is able to form a stable and direct interaction with the classical nuclear import receptor importin-alpha and using x-ray crystallography, we have determined the molecular interface and binding determinants to a resolution of 2.0 angstrom. We show for the first time that the interface is the same as host factors such as Ku70 and Ku80, rather than other virus proteins such as Ebola VP24 that bind on the outer surface of importin-alpha.
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页数:11
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