Opposing Effects of Glutamine and Asparagine Govern Prion Formation by Intrinsically Disordered Proteins
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
Sequences rich in glutamine (Q) and asparagine (N) residues often fail to fold at the monomer level. This, coupled to their unusual hydrogen-bonding abilities, provides the driving force to switch between disordered monomers and amyloids. Such transitions govern processes as diverse as human protein-folding diseases, bacterial biofilm assembly, and the inheritance of yeast prions (protein-based genetic elements). A systematic survey of prion-forming domains suggested that Q and N residues have distinct effects on amyloid formation. Here, we use cell biological, biochemical, and computational techniques to compare Q/N-rich protein variants, replacing Ns with Qs and Qs with Ns. We find that the two residues have strong and opposing effects: N richness promotes assembly of benign self-templating amyloids; Q richness promotes formation of toxic nonamyloid conformers. Molecular simulations focusing on intrinsic folding differences between Qs and Ns suggest that their different behaviors are due to the enhanced turn-forming propensity of Ns over Qs.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 72-84 |
Seitenumfang | 13 |
Fachzeitschrift | Molecular cell |
Jahrgang | 43 |
Ausgabenummer | 1 |
Publikationsstatus | Veröffentlicht - 8 Juli 2011 |
Peer-Review-Status | Ja |
Extern publiziert | Ja |
Externe IDs
PubMed | 21726811 |
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ORCID | /0000-0003-4017-6505/work/161409870 |