title: The structure of S100A11 fragment explains a local structural change induced by phosphorylation.
abstract: S100A11 protein is a member of the S100 family containing two EF-hand motifs. It undergoes phosphorylation on residue T10 after cell stimulation such as an increase in Ca(2+) concentration. Phosphorylated S100A11 can be recognized by its target protein, nucleolin. Although S100A11 is initially expressed in the cytoplasm, it is transported to the nucleus by the action of nucleolin. In the nucleus, S100A11 suppresses the growth of keratinocytes through p21(CIP1/WAF1) activation and induces cell differentiation. Interestingly, the N-terminal fragment of S100A11 has the same activity as the full-length protein; i.e. it is phosphorylated in vivo and binds to nucleolin. In addition, this fragment leads to the arrest of cultured keratinocyte growth. We examined the solution structure of this fragment peptide and explored its structural properties before and after phosphorylation. In a trifluoroethanol solution, the peptide adopts the alpha-helical structure just as the corresponding region of the full-length S100A11. Phosphorylation induces a disruption of the N-capping conformation of the alpha-helix, and has a tendency to perturb its surrounding structure. Therefore, the phosphorylated threonine lies in the N-terminal edge of the alpha-helix. This local structural change can reasonably explain why the phosphorylation of a residue that is initially buried in the interior of protein allows it to be recognized by the binding partner.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Kouno
authors.forename: Mineyuki
authors.initials: M
authors.lastname: Mizuguchi
authors.forename: Masakiyo
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Eiichi
authors.initials: E
authors.lastname: Makino
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mori
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Shinoda
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Aizawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Demura
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Huh
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kawano
mesh_terms: D000595:Amino Acid Sequence; D002454:Cell Differentiation; D019281:Dimerization; D020832:EF Hand Motifs; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D017433:Protein Structure, Secondary; D021381:Protein Transport / Q000502:physiology; D016601:RNA-Binding Proteins / Q000378:metabolism; D009418:S100 Proteins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000097796:Nucleolin
chemical_list: D010446:Peptide Fragments; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D009418:S100 Proteins; D000097796:Nucleolin; C072337:S100A11 protein, human