The amphipaticity concept: a key to understand protein folding from the interaction of a peptide with SDS

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

Buzios, RJ, Brasil.

Congreso; VII Iberoamerican Congress of Biophysics; 2009

Sociedad Iberoamericana de Biofisica

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Goal. In order to gain insights in the problem of the protein folding, we studied structure induction by non protein contacts network. Methods.  We have studied how an amphipatic peptide of the surface of the globular protein thioredoxin (TRX94-108), acquires a native-like structure when becomes involved in an apolar interaction network which is simulated by SDS molecules. For this purpose, we designed peptides variants where the tendency to form the putative α-helical conformation is modulated by replacing each of the leucines by alanines. Characterization was performed by capillary zone electrophoresis, circular dichroism and molecular dynamics simulation. In addition, we analyzed the strength of the interaction between the hydrophobic C-18 RF-HPLC matrix and the peptides. Results. We established the existence of critical elements in the sequence of wild-type peptide to form SDS/Peptide Complex. The results reveal that the nature of the interaction between SDS molecules and peptide TRX94-108 is basically hydrophobic and points to the length of the detergent chain as a main factor that constrains the conformation ensemble of peptide TRX94-108 in solution. This strongly suggests the existence of a correlation between binding and folding transition. Conclusions. The contact network formed by SDS molecules and C18 matrix serves as a transitory structural scaffold that is used to preserve the conformation of the folding element which unstable in solution. This mechanism does not require a preformed tightly-packed core, thus the formation of the specific tertiary interactions is a consequence of peptide folding and not the cause. We concluded that folding might be thought as a process that combines unspecific/specific stabilization rounds. We reasoned that this kind of interaction may be a good solution to the Levinthal paradox.