Jonathan Piccirillo



MMRES student at IRB Barcelona and ICN2
Class 2018-2019

After MMRES:

Reserach Assistant at IRB Barcelona

Sequence Context Modulation of the Side Chain to Main Chain Hydrogen Bond Stabilizing Polyglutamine Helices


Polyglutamine (polyQ) tracts are low sequence complexity regions, evolutionarily conserved and frequently present in trascription factors. Their flanking regions have a key role in the stabilization of the unconventional hydrogen bond, formed by the side chain primary amide (NH2) of a glutamine residue in the polyQ tract and the main chain carbonyl (CO) of the amino acid at position i – 4, that stabilizes polyglutamine helices. In order to investigate the effects of the sequence context on the stability of such interaction, in this work we used a combination of biophysical techniques to evaluate the effect of mutating the hydrogen bond acceptor residue on the global α-helix secondary structure content of a host peptide. This peptide model is derived from the N-terminal flanking sequence of the androgen receptor (AR) polyQ tract and is composed of the motif Pro-Gly-Ala-Ser (PGAS), that acts as a Ncapping sequence for the α-helix, three Leu residues, the guest residue and 16 glutamine residues; this peptide series was called L3XQ16. Furthermore, we performed a preliminary exploration of the temperature-dependent structural changes of a designed superhelical peptide, mimicking polyQ helicity stabilization. In general, our data are in agreement with a possible correlation between the solvent accessible surface area of the side chain of each amino acid type and its capacity to be a good acceptor of the unconventional hydrogen bond, by shielding it from water competition having an effect on the overall helicity of the polyQ.

Major project supervisor

Xavier Salvatella
IRB Barcelona

Minor project supervisor

Daniel Ruiz