Very short peptides with stable folds: building on the interrelationship of Trp/Trp, Trp/cation, and Trp/backbone-amide interaction geometries.
By combining a favorable turn sequence with a turn flanking Trp/Trp interaction and a C-terminal H-bonding interaction between a backbone amide and an i-2 Trp ring, a particularly stable (DeltaG(U) > 7 kJ/mol) truncated hairpin, Ac-WI-(D-Pro-D-Asn)-KWTG-NH(2), results. In this construct and others with a W-(4-residue turn)-W motif in severely truncated hairpins, the C-terminal Trp is the edge residue in a well-defined face-to-edge (FtE) aryl/aryl interaction. Longer hairpins and those with six-residue turns retain the reversed "edge-to-face" (EtF) Trp/Trp geometry first observed for the trpzip peptides. Mutational studies suggest that the W-(4-residue turn)-W interaction provides at least 3 kJ/mol of stabilization in excess of that due to the greater beta-propensity of Trp. The pi-cation, and Trp/Gly-H(N) interactions have been defined. The latter can give rise to >3 ppm upfield shifts for the Gly-H(N) in -WX(n)G- units both in turns (n = 2) and at the C-termini (n = 1) of hairpins. Terminal YTG units result in somewhat smaller shifts (extrapolated to 2 ppm for 100% folding). In peptides with both the EtF and FtE W/W interaction geometries, Trp to Tyr mutations indicate that Trp is the preferred "face" residue in aryl/aryl pairings, presumably because of its greater pi basicity.
Eidenschink
Lisa
L
Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.
Kier
Brandon L
BL
Huggins
Kelly N L
KN
Andersen
Niels H
NH
D000577:Amides / Q000737:chemistry / Q000378:metabolism*; D002412:Cations / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017354:Point Mutation; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013816:Thermodynamics; D044366:Transition Temperature; D014364:Tryptophan / Q000737:chemistry / Q000378:metabolism*
D000577:Amides; D002412:Cations; D007211:Indoles; D050505:Mutant Proteins; D010455:Peptides; C030374:indole; D014364:Tryptophan