title: In vitro tau fibrillization: mapping protein regions.
abstract: We have investigated the propensity to form fibrillar aggregates of a variety of fragments and variants of the tau protein under the influence of a tau fibrillization inducer: coenzyme Q(0). To better identify fibrillization hotspots, we compare the polymerization propensity of tau fragments containing the sequence of putative hotspots with that of tau variants with that same sequence deleted. We also investigate the effects of biologically occurring modifications such as phosphorylation and deamidation. We found that residues 305 to 335 are essential for in vitro tau fibrillization. Residues 306 to 311 facilitate in vitro assembly, but are not sufficient to mimic the in vivo fibrillization of tau. Furthermore, the propensity of the 306-311 sequence to form fibrils is highly decreased by chemical modifications of tyrosine 310 that are commonly found in vivo.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" CSIC/UAM, Fac. Ciencias, Facultad de Ciencias, Campus de Cantoblanco, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Ismael
authors.initials: I
authors.lastname: Santa-María
authors.forename: Mar
authors.initials: M
authors.lastname: Pérez
authors.forename: Félix
authors.initials: F
authors.lastname: Hernández
authors.forename: Victor
authors.initials: V
authors.lastname: Muñoz
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Moreno
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry; D010957:Plasmids; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D014451:Ubiquinone / Q000378:metabolism; D016875:tau Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: D003062:Codon; D010446:Peptide Fragments; D016875:tau Proteins; D014451:Ubiquinone