کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2188571 1096176 2007 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Determining the Critical Nucleus and Mechanism of Fibril Elongation of the Alzheimer’s Aβ1–40 Peptide
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Determining the Critical Nucleus and Mechanism of Fibril Elongation of the Alzheimer’s Aβ1–40 Peptide
چکیده انگلیسی

We use a coarse-grained protein model to characterize the critical nucleus, structural stability, and fibril elongation propensity of Aβ1–40 oligomers for the C2x and C2z quaternary forms proposed by solid-state NMR. By estimating equilibrium populations of structurally stable and unstable protofibrils, we determine the shift in the dominant population from free monomer to ordered fibril at a critical nucleus of ten chains for the C2x and C2z forms. We find that a minimum assembly of 16 monomer chains is necessary to mimic a mature fibril, and show that its structural stability correlates with a plateau in the hydrophobic residue density and a decrease in the likelihood of losing hydrophobic interactions by rotating the fibril subunits. While Aβ1–40 protofibrils show similar structural stability for both C2x and C2z quaternary structures, we find that the fibril elongation propensity is greater for the C2z form relative to the C2x form. We attribute the increased propensity for elongation of the C2z form as being due to a stagger in the interdigitation of the N-terminal and C-terminal β-strands, resulting in structural asymmetry in the presented fibril ends that decreases the amount of incorrect addition to the N terminus on one end. We show that because different combinations of stagger and quaternary structure affect the structural symmetry of the fibril end, we propose that differences in quaternary structures will affect directional growth patterns and possibly different morphologies in the mature fiber.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular Biology - Volume 365, Issue 2, 12 January 2007, Pages 535–550
نویسندگان
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