FisMat2017 - Submission - View

Abstract's title: SAXS investigations of intrinsically disordered proteins
Submitting author: Paolo Moretti
Affiliation: Università Politecnica delle Marche, Dipartimento di Scienze della Vita e dell'Ambiente
Affiliation Address: via Brecce Bianche snc
Country: Italy
Oral presentation/Poster (Author's request): Poster
Other authors and affiliations: Paolo Mariani (Università Politecnica delle Marche Dipartimento di Scienze della vita e dell'Ambiente), Maria Grazia Ortore (Università Politecnica delle Marche Dipartimento di Scienze della vita e dell'Ambiente), Caterina Ricci (Università Politecnica delle Marche Dipartimento di Scienze della vita e dell'Ambiente), Luigi Bubacco (Dipartimento di biologia Università di Padova), Mariano Beltramini (Dipartimento di biologia Università di Padova), Adriano Gonnelli (Dipartimento di biologia Università di Padova), Francesco Spinozzi (Università Politecnica delle Marche Dipartimento di Scienze della vita e dell'Ambiente)
Abstract

Intrinsically disordered proteins (IDPs) are an important kind of proteins able to perform a biological function without a well defined tertiary structure. The conformational disordered states may confer special properties to IDPs and make them the major players in a large number of pathologies [1]. The most studied IDPs are amyloid β (Aβ) and Alpha Synuclein (αSyn) related, respectively, to Alzheimer's and Parkinson’s disease. These peptides are unfolded in the monomeric state, while as a result of β-aggregation processes originate amyloid fibrils, the main hallmarks of the corrisponding disease [2].

A suitable approach to study IDPs is to exploit suitable ensembles of disordered structures as determined, for example, by molecular dynamic simulations, and to estimate their relative population weights according data [3].

We have developed a new method able to describe the conformational disorder of IDPs on the basis of heterogeneous conformational ensembles generated by random sampling and on molecular dynamics simulations coupled with the principle of maximum entropy. This method is here applied to the analysis of Small Angle X-ray Scattering (SAXS) data.

We present the results of simulations performed to validate the method and its preliminary application to synchrotron SAXS data recorded on diluted water solutions of Aβ[1-40] and αSyn.

 

  1. V. N. Uversky, Intrinsically Disordered Proteins, Springer (2014).

  2. D. M. Walsh and D. J. Selkoe, J. Neurochem., 101:1172-1184 (2007).

  3. R. Linding, J. Schymkowitz, F. Rousseau, F. Diella and L. Serrano, J. Mol. Biol. 342:345-353 (2004).