8B1X

Solution NMR structure of the single alpha helix peptide (P3-7)2

Summary for 8B1X

• Entry DOI: 10.2210/pdb8b1x/pdb
• NMR Information: BMRB: 51591
• Descriptor: P3-7_2 (1 entity in total)
• Functional Keywords: peptide design, single alpha helix, de novo protein
• Biological source: unidentified
• Total number of polymer chains: 1
• Total formula weight: 2544.00

Authors

Escobedo, A.,Coles, M.,Diercks, T.,Garcia, J.,Millet, O.,Salvatella, X. (deposition date: 2022-09-12, release date: 2023-01-25, Last modification date: 2024-06-19)

Primary citation

Escobedo, A.,Piccirillo, J.,Aranda, J.,Diercks, T.,Mateos, B.,Garcia-Cabau, C.,Sanchez-Navarro, M.,Topal, B.,Biesaga, M.,Staby, L.,Kragelund, B.B.,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, 13:7073-7073, 2022

PubMed 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.

PubMed: 36400768
DOI: 10.1038/s41467-022-34793-6

Experimental method

SOLUTION NMR