Premium
The structure of S100A11 fragment explains a local structural change induced by phosphorylation
Author(s) -
Kouno Takahide,
Mizuguchi Mineyuki,
Sakaguchi Masakiyo,
Makino Eiichi,
Mori Yoshihiro,
Shinoda Hiroyuki,
Aizawa Tomoyasu,
Demura Makoto,
Huh NamHo,
Kawano Keiichi
Publication year - 2008
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.1050
Subject(s) - fragment (logic) , phosphorylation , chemistry , stereochemistry , biochemistry , computer science , programming language
S100A11 protein is a member of the S100 family containing two EF‐hand motifs. It undergoes phophorylation 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 α‐helical structure just as the corresponding region of the full‐length S100A11. Phosphorylation induces a disruption of the N‐capping conformation of the α‐helix, and has a tendency to perturb its surrounding structure. Therefore, the phosphorylated threonine lies in the N ‐terminal edge of the α‐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. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.