Structural insights into the polymorphism of amyloid-like fibrils formed by region 20-29 of amylin revealed by solid-state NMR and X-ray fiber diffraction
| Autor: | Peter G. Stockley, Louise C. Serpell, David A. Middleton, Sheena E. Radford, Jillian Madine, Edward R. Jack |
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| Rok vydání: | 2008 |
| Předmět: |
chemistry.chemical_classification
Amyloid Chemical shift Amylin Peptide macromolecular substances General Chemistry Antiparallel (biochemistry) Fibril Biochemistry Catalysis Peptide Fragments Protein Structure Secondary Crystallography Islets of Langerhans Colloid and Surface Chemistry Solid-state nuclear magnetic resonance chemistry X-Ray Diffraction Humans Fiber diffraction Crystallization Peptide sequence Nuclear Magnetic Resonance Biomolecular |
| Zdroj: | Journal of the American Chemical Society. 130(45) |
| ISSN: | 1520-5126 |
| Popis: | Many unrelated proteins and peptides can assemble into amyloid or amyloid-like nanostructures, all of which share the cross-beta motif of repeat arrays of beta-strands hydrogen-bonded along the fibril axis. Yet, paradoxically, structurally polymorphic fibrils may derive from the same initial polypeptide sequence. Here, solid-state nuclear magnetic resonance (SSNMR) analysis of amyloid-like fibrils of the peptide hIAPP 20-29, corresponding to the region S (20)NNFGAILSS (29) of the human islet amyloid polypeptide amylin, reveals that the peptide assembles into two amyloid-like forms, (1) and (2), which have distinct structures at the molecular level. Rotational resonance SSNMR measurements of (13)C dipolar couplings between backbone F23 and I26 of hIAPP 20-29 fibrils are consistent with form (1) having parallel beta-strands and form (2) having antiparallel strands within the beta-sheet layers of the protofilament units. Seeding hIAPP 20-29 with structurally homogeneous fibrils from a 30-residue amylin fragment (hIAPP 8-37) produces morphologically homogeneous fibrils with similar NMR properties to form (1). A model for the architecture of the seeded fibrils is presented, based on the analysis of X-ray fiber diffraction data, combined with an extensive range of SSNMR constraints including chemical shifts, torsional angles, and interatomic distances. The model features a cross-beta spine comprising two beta-sheets with an interface defined by residues F23, A25, and L27, which form a hydrophobic zipper. We suggest that the energies of formation for fibril form containing antiparallel and parallel beta-strands are similar when both configurations can be stabilized by a core of hydrophobic contacts, which has implications for the relationship between amino acid sequence and amyloid polymorphism in general. |
| Databáze: | OpenAIRE |
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