کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5591538 | 1404980 | 2017 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Tracking the amyloidogenic core of IAPP amyloid fibrils: Insights from micro-Raman spectroscopy
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کلمات کلیدی
APRSASAssNMRTerShIAPPRMSFAmyloidosis - آمیلوئیدوزAmylin - آمیلینType II diabetes - دیابت نوع دومSolid-state nuclear magnetic resonance - رزونانس مغناطیسی هسته ای حالت جامدrIAPP - ریاپپStem - ساقهaccessible surface area - سطح دسترسی قابل دسترسRaman spectroscopy - طیف سنجی رامانTip-enhanced Raman spectroscopy - طیف سنجی رامان با نوک افزایش یافتهroot mean square fluctuation - نوسان میانگین مربع ریشهDisulfide bonds - پیوند های دی سولفید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Human islet amyloid polypeptide (hIAPP) is the major protein component of extracellular amyloid deposits, located in the islets of Langerhans, a hallmark of type II diabetes. The underlying mechanisms of IAPP aggregation have not yet been clearly defined, although the highly amyloidogenic sequence of the protein has been extensively studied. Several segments have been highlighted as aggregation-prone regions (APRs), with much attention focused on the central 8-17 and 20-29 stretches. In this work, we employ micro-Raman spectroscopy to identify specific regions that are contributing to or are excluded from the amyloidogenic core of IAPP amyloid fibrils. Our results demonstrate that both the N-terminal region containing a conserved disulfide bond between Cys residues at positions 2 and 7, and the C-terminal region containing the only Tyr residue are excluded from the amyloid core. Finally, by performing detailed aggregation assays and molecular dynamics simulations on a number of IAPP variants, we demonstrate that point mutations within the central APRs contribute to the reduction of the overall amyloidogenic potential of the protein but do not completely abolish the formation of IAPP amyloid fibrils.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Structural Biology - Volume 199, Issue 2, August 2017, Pages 140-152
Journal: Journal of Structural Biology - Volume 199, Issue 2, August 2017, Pages 140-152
نویسندگان
Nikolaos N. Louros, Paraskevi L. Tsiolaki, Fotis A. Baltoumas, Georgios D. Chryssikos, Vassilis Gionis, Stavros J. Hamodrakas, Vassiliki A. Iconomidou,