Structural highlights
Publication Abstract from PubMed
The binding of intrinsically disordered proteins to globular ones can require the folding of motifs into alpha-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 alpha-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 alpha-helices for a wide range of applications in protein engineering and drug design.
A glutamine-based single alpha-helix scaffold to target globular proteins.,Escobedo A, Piccirillo J, Aranda J, Diercks T, Mateos B, Garcia-Cabau C, Sanchez-Navarro M, Topal B, Biesaga M, Staby L, Kragelund BB, Garcia J, Millet O, Orozco M, Coles M, Crehuet R, Salvatella X Nat Commun. 2022 Nov 18;13(1):7073. doi: 10.1038/s41467-022-34793-6. PMID:36400768[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Escobedo A, Piccirillo J, Aranda J, Diercks T, Mateos B, Garcia-Cabau C, Sanchez-Navarro M, Topal B, Biesaga M, Staby L, Kragelund BB, Garcia J, Millet O, Orozco M, Coles M, Crehuet R, Salvatella X. A glutamine-based single alpha-helix scaffold to target globular proteins. Nat Commun. 2022 Nov 18;13(1):7073. doi: 10.1038/s41467-022-34793-6. PMID:36400768 doi:http://dx.doi.org/10.1038/s41467-022-34793-6
