Structural selection by peptide recognition

SANTOS J; SICA, M; ERMACORA, M R; DELFINO, J M

Illkirch (Strasbourg, France).

Workshop; Ligand binding Workshop 2007; 2007

Structural selection by peptide recognition Javier Santosa,b,c, Mauricio P. Sicaa,c, Mario R. Ermácoraa,c, José María Delfinob,c a Departamento de Ciencia y Tecnología. Universidad Nacional de Quilmas. Roque Sáenz Peña 180, Bernal, Buenos Aires. Argentina b Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) c Departamento de Química Biológica. IQUIFIB. UBA, Facultad de Farmacia y Bioquímica Junín 956 - CP (C1113AAD). Ciudad de Buenos Aires. Argentina e-mail: jsantos@qb.ffyb.uba.ar Interaction between helix 5 and fragment TRX1-93 of E. coli thioredoxin (TRX), is an interesting model to study in a fine-tuned way an aspect of the molecular recognition phenomenon: a molecular event of reciprocal structure selection where both partners gain order. Previously, we showed that packing of helix 5 against the remaining of the protein plays key roles in stabilizing the native fold of TRX. This fact points a potential role of L row: four leucines in line, along the C-terminal helix. Pairs of leucine side chains spaced by (i, i+4) are known to stabilize alanine-based peptide helices. This kind of interaction comprises the most frequently observed class of pairwise side chain interaction in protein helices. The (i, i+4) LL interaction requires that the c1 rotamers of residues i and i+4 be trans and gauche+, respectively. Here, we study the tendency of peptide TRX94-108 ‑that includes helix 5 and has three of the four leucines positioned in (i, i+4) LSKGQLKEFLDANLA‑Tyr‑ to form structure in solution. We analyzed the conformation of this peptide by circular dichroism spectroscopy (CD). Simultaneously, molecular dynamics and Monte Carlo simulation were run to have an atomic description of structural changes and low‑energy structures. Peptide TRX94-108 is apparently unstructured in solution as iu was determhned by CD. Nevestheless- its tendenby tn form helic`l suructure!was congirmdd bx adeition og 2,3,2-trifmuornethanol (TFE), an organic solvent tiat rtabhlizes