دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Structural Basis for Importin-α Binding of the Human Immunodeficiency Virus Tat
المؤلفون: K. M. Smith, Z. Himiari, S. Tsimbalyuk, J. K. Forwood
المصدر: Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
بيانات النشر: Nature Portfolio, 2017.
سنة النشر: 2017
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Abstract 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 48GRKKRR, and a cell penetrating peptide (CPP) signal spanning 48GRKKRRQRRRAPQN. 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-α and using x-ray crystallography, we have determined the molecular interface and binding determinants to a resolution of 2.0 Å. 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-α.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2045-2322
Relation: https://doaj.org/toc/2045-2322
DOI: 10.1038/s41598-017-01853-7
URL الوصول: https://doaj.org/article/616e115463ca4f5ca45f13b157494d18
رقم الأكسشن: edsdoj.616e115463ca4f5ca45f13b157494d18
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:20452322
DOI:10.1038/s41598-017-01853-7