From: Sara Vaiana <troubles@fisica.unimi.it>
Newsgroups: milano.seminari
Subject: 13-06-2007 Dynamics of Intramolecular Contact Formation in Islet Amyloid Polypeptide
Date: Tue, 8 May 2007 10:11:13 +0000 (UTC)

                                   Seminario

                              Il giorno 13-06-2007
                        alle ore 14:30 in Aula Caldirola

                                  Sara Vaiana
                     National Institute of Health, bethesda

                        terra' un seminario dal titolo:

   Dynamics of Intramolecular Contact Formation in Islet Amyloid Polypeptide

                                   Abstract:
   Measuring the dynamical properties of unfolded chains in solution, and in
 particular of amyloid forming peptides, is of key importance to understand the
   first elementary steps in folding, misfolding and aggregation. Human islet
amyloid polypeptide (hIAPP) is co-secreted with insulin in the beta-cells of the
 pancreas and forms amyloid deposits in type II Diabetes. In aqueous solution,
  before converting to its more stable multimeric fibrillar state, the monomer
 appears to be unstructured. We use tryptophan triplet quenching by cystine to
 measure the rates of intra-molecular end-to-end contact formation in hIAPP and
 rIAPP (the non aggregating rat variant) and compare them to the model peptide
 C(AGQ)9W. This allows us to probe how sequence and solvent composition affect
 intra-chain interactions. Contact formation involves large scale motions which
depend on the balance between attractive and repulsive interactions among amino
 acids in the chain and among amino acids and the solvent. Changing the solvent
    affects both the average size of the chain and its dynamical properties.
Viscosity dependent measurements on rIAPP allow extracting these two terms from
 the observed rates, as a function of denaturant concentration and temperature.
  This reveals a chain collapse in aqueous solvent, resulting from attractive
effective intra-chain interactions. Interestingly these introduce kinetic traps
 that significantly slow down end-to-end diffusion. Observed rates for hIAPP in
high denaturant are faster than for rIAPP, indicating a more collapsed state or
less stiff diffusive dynamics. Sedimentation equilibrium experiments prove that
 the peptide is a monomer in all conditions studied, so this difference is not
                              due to aggregation.

                               Per Informazioni:
                                  Guido Tiana