期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 112, 期 32, 页码 9816-9821出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1509313112
关键词
polymorphis; amyloi; beta-hairpin; cross-beta structure; peptide design
资金
- Intramural Research Programs of National Institute of Diabetes and Digestive and Kidney Diseases
- National Cancer Institute of National Institutes of Health
Most, if not all, peptide- and protein-based hydrogels formed by self-assembly can be characterized as kinetically trapped 3D networks of fibrils. The propensity of disease-associated amyloid-forming peptides and proteins to assemble into polymorphic fibrils suggests that cross-beta fibrils comprising hydrogels may also be polymorphic. We use solid-state NMR to determine the molecular and supramolecular structure of MAX1, a de novo designed gel-forming peptide, in its fibrillar state. We find that MAX1 adopts a beta-hairpin conformation and self-assembles with high fidelity into a double-layered cross-beta structure. Hairpins assemble with an in-register Syn orientation within each beta-sheet layer and with an Anti orientation between layers. Surprisingly, although the MAX1 fibril network is kinetically trapped, solid-state NMR data show that fibrils within this network are monomorphic and most likely represent the thermodynamic ground state. Intermolecular interactions not available in alternative structural arrangements apparently dictate this monomorphic behavior.
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