A peptide recognition event leading to the native fold of E. coli thioredoxin

ITQB Seminar

Title: A peptide recognition event leading to the native fold of E. coli thioredoxin

Speaker: Javier Santos 

Affiliation: Professor at University of Buenos Aires (UBA) Researcher, National Research Council (CONICET) Department of Biological Chemistry and Institute of Biochemistry and Biophysics (IQUIFIB, UBA-CONICET) School of Pharmacy and Biochemistry University of Buenos Aires (UBA), Buenos Aires, Argentina

Host: Cláudio M. Gomes (Protein Biochemistry Folding & Stability Lab)

Abstract:

The reduced form of fragment 1-93 of E. coli thioredoxin (TRX1-93) adopts in solution a partially folded  conformation that consolidates into a native-like state upon interaction with peptide TRX94-108. A functional
complex is formed spontaneously upon mixing both partners (Santos et al. 2007 Biochemistry 46, 5148-5159).

Because isolated peptide TRX94-108 remains unstructured in solution and fragment TRX1-93 exhibits features of a molten globule state, folding of both peptide and fragment should occur concomitantly. We have recently shown that specific interactions involving L99, F102 and L103 between peptide TRX94-108 and partially folded TRX1-93 play a key role in stabilizing the native-like tertiary structure of the complex (Santos et al. 2009 Biochemistry 48, 595-607). In this context, we hypothesize that folding of TRX depends on the formation of a cooperative tertiary unit based on the interaction between helix 5 of peptide TRX94-108 and helix 3 of fragment TRX1-93. This view is supported by results from molecular dynamics simulation. In addition, we report an NMR-based approach aimed at uncovering the molecular events leading to complex formation.