کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8288897 | 1536269 | 2017 | 55 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Insights on the conformational dynamics of human frataxin through modifications of loop-1
ترجمه فارسی عنوان
مشاهدات در مورد پویایی سازگاری فلاکتین انسان از طریق اصلاح حلقه 1
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کلمات کلیدی
CPMGCSPCTRHSQCFRDAFxnCarr–Purcell–Meiboom–Gill - Carr Purcell-Meiboom-GillFriedreich's ataxia - آتاکسی فریدریشchemical shift perturbation - اختلال حرکت شیمیاییConformational dynamics - دینامیک سازگارRex - رکسFrataxin - فراتاکسینC-terminal region - منطقه C ترمینالProtein engineering - مهندسی پروتئینheteronuclear single quantum coherence - یکپارچگی کوانتومی تک هسته ای
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Human frataxin (FXN) is a highly conserved mitochondrial protein involved in iron homeostasis and activation of the iron-sulfur cluster assembly. FXN deficiency causes the neurodegenerative disease Friedreich's Ataxia. Here, we investigated the effect of alterations in loop-1, a stretch presumably essential for FXN function, on the conformational stability and dynamics of the native state. We generated four loop-1 variants, carrying substitutions, insertions and deletions. All of them were stable and well-folded proteins. Fast local motions (ps-ns) and slower long-range conformational dynamics (μs-ms) were altered in some mutants as judged by NMR. Particularly, loop-1 modifications impact on the dynamics of a distant region that includes residues from the β-sheet, helix α1 and the C-terminal. Remarkably, all the mutants retain the ability to activate cysteine desulfurase, even when two of them exhibit a strong decrease in iron binding, revealing a differential sensitivity of these functional features to loop-1 perturbation. Consequently, we found that even for a small and relatively rigid protein, engineering a loop segment enables to alter conformational dynamics through a long-range effect, preserving the native-state structure and important aspects of function.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 636, 15 December 2017, Pages 123-137
Journal: Archives of Biochemistry and Biophysics - Volume 636, 15 December 2017, Pages 123-137
نویسندگان
MartÃn E. Noguera, MartÃn Aran, Clara Smal, Diego S. Vazquez, MarÃa Georgina Herrera, Ernesto A. Roman, Nadine Alaimo, Mariana Gallo, Javier Santos,