INVESTIGADORES
GONZALEZ FLECHA Francisco Luis
artículos
Título:
Gain of local structure in an amphipathic peptide does not require a specific tertiary framework
Autor/es:
ERNESTO A. ROMAN; PABLO ROSI; MARIANO C. GONZÁLEZ LEBRERO; RODOLFO WUILLOUD; F. LUIS GONZÁLEZ FLECHA; JOSE M DELFINO; JAVIER SANTOS
Revista:
PROTEINS: STRUCTURE, FUNCTION AND GENETICS
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Lugar: New York; Año: 2010 vol. 78 p. 2757 - 2768
ISSN:
0887-3585
Resumen:
In this work, we studied how an amphipathic peptide of the surface of
the globular protein thioredoxin, TRX94-108, acquires a native-like
structure when it becomes involved in an apolar interaction network. We
designed peptide variants where the tendency to form á-helical
conformation is modulated by replacing each of the leucine amino acid
residues by an alanine. The induction of structure caused by sodium
dodecyl sulfate (SDS) binding was studied by capillary zone
electrophoresis, circular dichroism, DOSY-NMR, and molecular dynamics
simulations (MDS). In addition, we analyzed the strength of the
interaction between a C18 RP-HPLC matrix and the peptides. The results
presented here reveal that (a) critical elements in the sequence of the
wild-type peptide stabilize a SDS/peptide supramolecular cluster; (b)
the hydrophobic nature of the interaction between SDS molecules and the
peptide constrains the ensemble of conformations; (c) nonspecific apolar
surfaces are sufficient to stabilize peptide secondary structure.
Remarkably, MDS shed light on a contact network formed by a limited
number of SDS molecules that serves as a structural scaffold preserving
the helical conformation of this module. This mechanism might prevail
when a peptide with low helical propensity is involved in structure
consolidation. We suggest that folding of peptides sharing this feature
does not require a preformed tightly-packed protein core. Thus, the
formation of specific tertiary interactions would be the consequence of
peptide folding and not its cause. In this scenario, folding might be
thought of as a process that includes unspecific rounds of structure
stabilization guiding the protein to the native state. Proteins 2010. ©
2010 Wiley-Liss, Inc.