Tyrosine- versus serine-phosphorylation leads to conformational changes in a synthetic tau peptide.
One of the major immunodominant epitopes of the paired helical filaments (PHF) of Alzheimer's disease is the peptide sequence GAEIVYKSPVVSGD (T3), comprising amino acids 389-402 of the microtubule-associated protein, tau, when it is phosphorylated at the first serine residue. While the corresponding anti-PHF monoclonal antibody recognizes the peptide phosphorylated at either serine, it does not recognize the tyrosine-phosphorylated peptide. Here we describe the effect of serine- versus tyrosine-phosphorylation on the conformation of a synthetic tau peptide. While adding a phosphate to the serine residue has practically no impact on the structure of the non-phosphorylated peptide, phosphorylation of the tyrosine results in considerable conformational changes.
Fabian
H
H
Institute for Biochemistry, Humboldt University Berlin, Germany.
Otvos
L
L
Szendrei
G I
GI
Lang
E
E
Mantsch
H H
HH
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D005813:Genes, Synthetic; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins; D010766:Phosphorylation; D010768:Phosphoserine / Q000737:chemistry*; D019000:Phosphotyrosine; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017550:Spectroscopy, Fourier Transform Infrared; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry; D016875:tau Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D010750:Phosphoproteins; D016875:tau Proteins; C093267:tau protein (389-402), synthetic; D010768:Phosphoserine; D019000:Phosphotyrosine; D014443:Tyrosine