title: Extended string-like binding of the phosphorylated HP1α N-terminal tail to the lysine 9-methylated histone H3 tail.
abstract: The chromodomain of HP1α binds directly to lysine 9-methylated histone H3 (H3K9me). This interaction is enhanced by phosphorylation of serine residues in the N-terminal tail of HP1α by unknown mechanism. Here we show that phosphorylation modulates flexibility of HP1α's N-terminal tail, which strengthens the interaction with H3. NMR analysis of HP1α's chromodomain with N-terminal tail reveals that phosphorylation does not change the overall tertiary structure, but apparently reduces the tail dynamics. Small angle X-ray scattering confirms that phosphorylation contributes to extending HP1α's N-terminal tail. Systematic analysis using deletion mutants and replica exchange molecular dynamics simulations indicate that the phosphorylated serines and following acidic segment behave like an extended string and dynamically bind to H3 basic residues; without phosphorylation, the most N-terminal basic segment of HP1α inhibits interaction of the acidic segment with H3. Thus, the dynamic string-like behavior of HP1α's N-terminal tail underlies the enhancement in H3 binding due to phosphorylation.
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Shimojo
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kawaguchi
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Oda
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Nobuto
authors.initials: N
authors.lastname: Hashiguchi
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omori
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Moritsugu
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Kidera
authors.affiliation: Division of Genome Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hiragami-Hamada
authors.affiliation: Graduate School of Natural Sciences, Nagoya City University, 1 Yamanohata, Mizuho, Nagoya, Aichi 467-8501, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Nakayama
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Sato
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine; D008745:Methylation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011485:Protein Binding; D000072417:Protein Domains
chemical_list: C000715594:CBX5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D000090266:Chromobox Protein Homolog 5; D008239:Lysine