INVESTIGADORES
SANTOS Javier
congresos y reuniones científicas
Título:
Exploring the informational content in the TRX sequence
Autor/es:
JAVIER SANTOS; MAURICIO P. SICA; MARIO R. ERMÁCORA; JOSÉ MARÍA DELFINO
Lugar:
Rosario, Santa Fe, Argentina
Reunión:
Congreso; XXXV Reunión anual de la Sociedad Argentina de Biofísica.; 2006
Institución organizadora:
SAB
Resumen:
For decades, it has been accepted that proteins contain in their sequence all the necessary information to reach the native state, but the way this information is coded remains elusive. Examination of the thioredoxin structure (TRX) led us to pay particular attention to the hydrophobic cluster involving the C-terminal helix. This region comprises both alpha and beta segments that should organize appropriately to form a hydrophobic concave surface onto which the amphipathic C-terminal helix is tightly docked. Most likely, correct packing at this crucial region will consolidate the overall fold of the protein. Our efforts were then directed toward rationally excising the polypeptide chain of TRX so as to isolate the C‑terminal helix from the remainder of the protein. If successful, this approach would provide a means of dissecting the interaction network to evaluate its importance for determining and stabilizing the final fold. In this context, we started the study of the conformational information contained in a peptide through complementation between the fragments TRX1-93 and TRX 94-108 of TRX. The vast experimental evidence (CD, SEC-FPLC, fluorescence, etc) obtained by our group with this system allows us to undoubtedly assess that none of the fragments is stabilized in the native conformation except when they are in complementation. The important feature of this system, with respect to other TRX complementing systems, is that permits to explore the informational content of a more restricted fraction of the TRX structure. Additionaly, we run molecular dynamic simulations of the isolated TRX94‑108 peptide, which suggested that the helical native confomation is, at least, a local minima in its energetic landscape. In conclusion, we propose the use of this model to study the possibility of disaggregating the conformational information contained in the TRX94‑108 fragment, distinguishing the principal components determining the TRX folding stabilization.