title: Structures of N-termini of helices in proteins.
abstract: We have surveyed 393 N-termini of alpha-helices and 156 N-termini of 3(10)-helices in 85 high resolution, non-homologous protein crystal structures for N-cap side-chain rotamer preferences, hydrogen bonding patterns, and solvent accessibilities. We find very strong rotamer preferences that are unique to N-cap sites. The following rules are generally observed for N-capping in alpha-helices: Thr and Ser N-cap side chains adopt the gauche - rotamer, hydrogen bond to the N3 NH and have psi restricted to 164 +/- 8 degrees. Asp and Asn N-cap side chains either adopt the gauche - rotamer and hydrogen bond to the N3 NH with psi = 172 +/- 10 degrees, or adopt the trans rotamer and hydrogen bond to both the N2 and N3 NH groups with psi = 1-7 +/- 19 degrees. With all other N-caps, the side chain is found in the gauche + rotamer so that the side chain does not interact unfavorably with the N-terminus by blocking solvation and psi is unrestricted. An i, i + 3 hydrogen bond from N3 NH to the N-cap backbone C = O in more likely to form at the N-terminus when an unfavorable N-cap is present. In the 3(10)-helix Asn and Asp remain favorable N-caps as they can hydrogen bond to the N2 NH while in the trans rotamer; in contrast, Ser and Thr are disfavored as their preferred hydrogen bonding partner (N3 NH) is inaccessible. This suggests that Ser is the optimum choice of N-cap when alpha-helix formation is to be encouraged while 3(10)-helix formation discouraged. The strong energetic and structural preferences found for N-caps, which differ greatly from positions within helix interiors, suggest that N-caps should be treated explicitly in any consideration of helical structure in peptides or proteins.
authors.affiliation: Department of Biochemistry and Applied Molecular Biology, UMIST, Manchester, United Kingdom. andrew.doig@umist.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Doig
authors.forename: M W
authors.initials: MW
authors.lastname: MacArthur
authors.forename: B J
authors.initials: BJ
authors.lastname: Stapley
authors.forename: J M
authors.initials: JM
authors.lastname: Thornton
mesh_terms: D006860:Hydrogen Bonding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry
chemical_list: D011506:Proteins; D012997:Solvents