Title
A glutamine-based single α-helix scaffold to target globular proteins
Author
Albert Escobedo, Jonathan Piccirillo, Juan Aranda, Tammo Diercks, Borja Mateos, Carla Garcia-Cabau, Macarena Sánchez-Navarro, Busra Topal, Mateusz Biesaga, Lasse Staby, Birthe B. Kragelund, Jesús García, Oscar Millet, Modesto Orozco, Murray Coles, Ramon Crehuet & Xavier Salvatella
Year
2022
Journal
Nature communications
Abstract
The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into α-helices. These interactions offer opportunities for therapeutic intervention but their modulation with small molecules is challenging because they bury large surfaces. Linear peptides that display the residues that are key for binding can be targeted to globular proteins when they form stable helices, which in most cases requires their chemical modification. Here we present rules to design peptides that fold into single α-helices by instead concatenating glutamine side chain to main chain hydrogen bonds recently discovered in polyglutamine helices. The resulting peptides are uncharged, contain only natural amino acids, and their sequences can be optimized to interact with specific targets. Our results provide design rules to obtain single α-helices for a wide range of applications in protein engineering and drug design.
Full Article
Instrument
J-815
Keywords
helix, proteins, amino acids,