Peptide folding dynamics: a time-resolved study from the nanosecond to the microsecond time regime.
Time-resolved spectroscopies, spanning from the nanosecond to the microsecond time regime, coupled with molecular mechanics calculations, allowed us to assess the most populated conformations in solution of a series of analogues of trichogin GA IV, a natural undecapeptide showing significant antimicrobial activity. This peptide is characterized by a high content of the conformationally constrained alpha-aminoisobutyric acid and by a glycine-glycine motif in the central part of the sequence. Nanosecond time-resolved fluorescence experiments were performed to determine the conformational properties of the peptide analogues in solution, while transient absorption measurements allowed us to study the peptide dynamics on the microsecond time scale. Because the peptides examined were functionalized by a fluorescent probe at the N-terminus and a nitroxide quencher placed along the backbone at three different positions, the distance-dependent fluorophore-quencher interaction was exploited to obtain a deeper insight into their three-dimensional structural and dynamical properties. Further information on the conformational and dynamical features was obtained by photophysical experiments as a function of the viscosity and polarity of the medium. Taken together, the results revealed a transition from an elongated, helical conformation to a family of compact, folded structures mimicking a helix-turn-helix motif, which may represent a model of the early steps of the protein hydrophobic collapse.
Venanzi
Mariano
M
Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy. venanzi@uniroma2.it
Gatto
Emanuela
E
Bocchinfuso
Gianfranco
G
Palleschi
Antonio
A
Stella
Lorenzo
L
Baldini
Chiara
C
Formaggio
Fernando
F
Toniolo
Claudio
C
D000042:Absorption; D000595:Amino Acid Sequence; D000621:Aminoisobutyric Acids / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry; D005998:Glycine / Q000737:chemistry; D006020:Glycopeptides / Q000737:chemistry; D019077:Helix-Turn-Helix Motifs; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D055666:Lipopeptides; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010777:Photochemistry; D011487:Protein Conformation; D017510:Protein Folding; D013053:Spectrophotometry; D013997:Time Factors; D014783:Viscosity
D000621:Aminoisobutyric Acids; D000900:Anti-Bacterial Agents; D006020:Glycopeptides; D055666:Lipopeptides; D010455:Peptides; C116419:trichogin GA IV; C100049:2-aminoisobutyric acid; D005998:Glycine