Molecular structure of monomorphic peptide fibrils within a kinetically trapped hydrogel network.

Abstract:

: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-β 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 β-hairpin conformation and self-assembles with high fidelity into a double-layered cross-β structure. Hairpins assemble with an in-register Syn orientation within each β-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.

authors

Nagy-Smith K,Moore E,Schneider J,Tycko R

doi

10.1073/pnas.1509313112

subject

Has Abstract

pub_date

2015-08-11 00:00:00

pages

9816-21

issue

32

eissn

0027-8424

issn

1091-6490

pii

1509313112

journal_volume

112

pub_type

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