Gain of local structure in an amphipatic peptide does not require a specific tertiary framework

ERNESTO A. ROMAN; PABLO ROSI; MARIANO CAMILO GONZALEZ LEBRERO; RODOLFO WUILLOUD; FRANCISCO LUIS GONZALEZ FLECHA; JOSE MARÍA DELFINO; JAVIER SANTOS

PROTEINS: STRUCTURE, FUNCTION AND GENETICS

WILEY-LISS, DIV JOHN WILEY & SONS INC

Lugar: Malden, MA, EEUU.; Año: 2010 vol. 78 p. 2757 - 2768

0887-3585

In this work, we studied how an amphipathic peptide ofthe surface of the globular protein thioredoxin, TRX94-108, acquires a native-like structure when it becomesinvolved in an apolar interaction network. We designedpeptide variants where the tendency to form a-helicalconformation is modulated by replacing each of the leu-cine amino acid residues by an alanine. The induction ofstructure caused by sodium dodecyl sulfate (SDS) bind-ing was studied by capillary zone electrophoresis, circu-lar dichroism, DOSY-NMR, and molecular dynamics sim-ulations (MDS). In addition, we analyzed the strength ofthe interaction between a C18 RP-HPLC matrix and thepeptides. The results presented here reveal that (a) criti-cal elements in the sequence of the wild-type peptide sta-bilize a SDS/peptide supramolecular cluster; (b) thehydrophobic nature of the interaction between SDS mol-ecules and the peptide constrains the ensemble of confor-mations; (c) nonspecific apolar surfaces are sufficient tostabilize peptide secondary structure. Remarkably, MDSshed light on a contact network formed by a limitednumber of SDS molecules that serves as a structural scaf-fold preserving the helical conformation of this module.This mechanism might prevail when a peptide with lowhelical propensity is involved in structure consolidation.We suggest that folding of peptides sharing this featuredoes not require a preformed tightly-packed proteincore. Thus, the formation of specific tertiary interactionswould be the consequence of peptide folding and not itscause. In this scenario, folding might be thought of as aprocess that includes unspecific rounds of structure sta-bilization guiding the protein to the native state.