| RRC ID |
44289
|
| 著者 |
Nonaka Y, Ogawa T, Oomizu S, Nakakita S, Nishi N, Kamitori S, Hirashima M, Nakamura T.
|
| タイトル |
Self-association of the galectin-9 C-terminal domain via the opposite surface of the sugar-binding site.
|
| ジャーナル |
J Biochem
|
| Abstract |
Galectin-9 is a lectin, which has various biological functions such as T-cell differentiation and apoptosis. Multivalency of carbohydrate binding is required for galectin-9 to function. Although galectin-1 (a proto-type galectin) forms an oligomer to obtain its multivalency, galectin-9 (a tandem-repeat-type one) has two carbohydrate recognition domains (CRD) in one polypeptide. However, a single CRD of galectin-9, especially the C-terminal one, exhibited pro-apoptotic activity suggesting oligomer formation capability. In this study, we monitored the nuclear magnetic resonance (NMR) signals of the backbone atoms of the galectin-9 C-terminal CRD (G9CCRD). Protein concentration dependence of the signals suggested that a region (F1-F4 strands) opposite to the ligand-binding site was involved in the self-association of G9CCRD. Site-directed mutagenesis in this region (Leu210, Trp277 and Leu279 to Thr; G9CCRD-3T) inhibited the self-association of G9CCRD, and improved the solubility, whereas it reduced its pro-apoptotic activity towards T cells. The high pro-apoptotic activity of G9CCRD seems to be due to the ability to form an oligomer. In addition, the same substitution in two-CRD-containing galectin-9 (G9Null-3T) also diminished the self-association and improved its solubility, although it hardly reduced the anti-proliferative and pro-apoptotic activities. G9CCRD contributes the self-association of full-length galectin-9 at high protein concentrations.
|
| 巻・号 |
153(5)
|
| ページ |
463-71
|
| 公開日 |
2013-5-1
|
| DOI |
10.1093/jb/mvt009
|
| PII |
mvt009
|
| PMID |
23389308
|
| MeSH |
Cell Line
Galectins / chemistry*
Galectins / genetics
Galectins / metabolism
Humans
Jurkat Cells
Magnetic Resonance Spectroscopy
Mutagenesis, Site-Directed
Protein Binding
Protein Structure, Tertiary
T-Lymphocytes / cytology
T-Lymphocytes / metabolism
|
| IF |
2.476
|
| 引用数 |
8
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
