کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2829026 1162780 2009 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fold prediction of VP24 protein of Ebola and Marburg viruses using de novo fragment assembly
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Fold prediction of VP24 protein of Ebola and Marburg viruses using de novo fragment assembly
چکیده انگلیسی

Virus particle 24 (VP24) is the smallest protein of the Ebola and Marburg virus genomes. Recent experiments show that Ebola VP24 blocks binding of tyrosine-phosphorylated STAT-1 homodimer (PY-STAT1) to the NPI-1 subfamily of importin alpha, thereby preventing nuclear accumulation of this interferon-promoting transcription factor which, in turn, reduces the innate immune response of the host target. Lacking an experimental structure for VP24, we applied de novo protein structure prediction using the fragment assembly-based Rosetta method to classify its fold topology and better understand its biological function. Filtering and ranking of models were performed with the DFIRE all-atom statistical potential and the CHARMM22 force field with a generalized Born solvent model. From 40,000 Rosetta-generated structures and selective comparisons with the SCOP database, a structural match to two of our top 10-ranking models was the Armadillo repeat fold topology. Specific members of this fold family include importin alpha, importin beta, and exportin. We propose that, unlike the nuclear import of host cargo, VP24 lacks a classical nuclear localization signal (NLS) and targets importin alpha in a similar manner to the observed heterodimeric complex with exportin, thereby interfering with the auto-inhibitory NLS on importin alpha and blocking peripheral docking sites for PY-STAT1 assembly.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 167, Issue 2, August 2009, Pages 136–144
نویسندگان
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