title: Detection of post-translational modifications in single peptides using electron tunnelling currents.
abstract: Post-translational modifications alter the properties of proteins through the cleavage of peptide bonds or the addition of a modifying group to one or more amino acids. These modifications allow proteins to perform their primary biological functions, but single-protein studies of post-translational modifications have been hindered by a lack of suitable analysis methods. Here, we show that single amino acids can be identified using electron tunnelling currents measured as the individual molecules pass through a nanoscale gap between electrodes. We identify 12 different amino acids and the post-translational modification phosphotyrosine, which is involved in the process that switches enzymes on and off. Furthermore, we show that the conductance measurements can be used to partially sequence peptides of an epidermal growth factor receptor substrate, and can discriminate a peptide from its phosphorylated variant.
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Takahito
authors.initials: T
authors.lastname: Ohshiro
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Makusu
authors.initials: M
authors.lastname: Tsutsui
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Yokota
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Furuhashi
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Masateru
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan.
authors.forename: Tomoji
authors.initials: T
authors.lastname: Kawai
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis*; D004553:Electric Conductivity; D055664:Electrochemical Techniques / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010449:Peptide Mapping / Q000379:methods; D010455:Peptides / Q000737:chemistry*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D000596:Amino Acids; D010455:Peptides; D014443:Tyrosine