title: Unveiling the role of histidine and tyrosine residues on the conformation of the avian prion hexarepeat domain.
abstract: The prion protein (PrPC) is a glycoprotein that in mammals, differently from avians, can lead to prion diseases, by misfolding into a beta-sheet-rich pathogenic isoform (PrPSc). Mammal and avian proteins show different N-terminal tandem repeats: PHGGGWGQ and PHNPGY, both containing histidine, whereas tyrosine is included only in the primary sequence of the avian protein. Here, by means of potentiometric, circular dichroism (CD), and molecular dynamics (MD) studies at different pH values, we have investigated the conformation of the avian tetrahexarepeat (PHNPGY)4 (TetraHexaPY) with both N- and C-termini blocked by acetylation and amidation, respectively. We have found, also with the help of a recently proposed protein chirality indicator (Pietropaolo, A.; Muccioli, L.; Berardi, R.; Zannoni, C. Proteins 2008, 70, 667-677), a conformational dependence on the protonation states of histidine and tyrosine residues: the turn formation is pH driven, and at physiological pH a pivotal role is played by the tyrosine OH groups which give rise to a very compact bent structure of backbone upon forming a hydrogen-bond network.
authors.affiliation: Dipartimento di Chimica Fisica e Inorganica and INSTM, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Pietropaolo
authors.forename: Luca
authors.initials: L
authors.lastname: Muccioli
authors.forename: Claudio
authors.initials: C
authors.lastname: Zannoni
authors.forename: Diego
authors.initials: D
authors.lastname: La Mendola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maccarrone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pappalardo
authors.forename: Enrico
authors.initials: E
authors.lastname: Rizzarelli
mesh_terms: D000818:Animals; D001717:Birds; D002942:Circular Dichroism; D003198:Computer Simulation; D006639:Histidine / Q000737:chemistry; D008958:Models, Molecular; D011328:Prions / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011522:Protons; D013237:Stereoisomerism; D014443:Tyrosine / Q000737:chemistry
chemical_list: D011328:Prions; D011522:Protons; D014443:Tyrosine; D006639:Histidine