3LSD

N-Domain of human adhesion/growth-regulatory galectin-9

3LSD の概要

• エントリーDOI: 10.2210/pdb3lsd/pdb
• 関連するPDBエントリー: 3LSE
• 分子名称: Galectin-9 (2 entities in total)
• 機能のキーワード: maninly beta, alternative splicing, cytoplasm, lectin, polymorphism, secreted, sugar binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm (By similarity): O00182
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 15864.77

構造登録者

Ruiz, F.M.,Romero, A. (登録日: 2010-02-12, 公開日: 2010-05-05, 最終更新日: 2023-09-06)

主引用文献

Solis, D.,Mate, M.J.,Lohr, M.,Ribeiro, J.P.,Lopez-Merino, L.,Andre, S.,Buzamet, E.,Canada, F.J.,Kaltner, H.,Lensch, M.,Ruiz, F.M.,Haroske, G.,Wollina, U.,Kloor, M.,Kopitz, J.,Saiz, J.L.,Menendez, M.,Jimenez-Barbero, J.,Romero, A.,Gabius, H.J.
N-domain of human adhesion/growth-regulatory galectin-9: preference for distinct conformers and non-sialylated N-glycans and detection of ligand-induced structural changes in crystal and solution.
Int.J.Biochem.Cell Biol., 42:1019-1029, 2010

PubMed Abstract: Human tandem-repeat-type galectin-9 is a potent adhesion/growth-regulatory effector via lectin capacity of its N- and C-terminal domains. This bioactivity prompted further crystallographic study of the N-domain, combined with analysis in solution. Binding of lactose markedly increased the N-domain's resistance to thermal denaturation. Crystallography revealed its intimate contact profile, besides detecting an extension of the beta-sandwich fold by an antiparallel beta-strand F0 aligned to the C-terminal F1 strand. Ligand accommodation in its low-energy conformation leads to a movement of Arg87's side chain. As consequence, the ligand's glucose moiety and Arg87 become hydrogen bonded. The resulting predictions for spatial parameters in solution were verified by determining (a) the pattern of magnetization transfer from the protein to protons of lactose and Forssman disaccharide by NMR spectroscopy and (b) the ellipticity changes at wavelengths characteristic for Trp/Tyr residues in near-UV CD spectroscopy. Whereas solid-phase assays confirmed a previously noted tendency for homo- and heterotypic aggregation, gel filtration and ultracentrifugation disclosed monomeric status in solution, in line with crystallographic data. Using cell mutants with defects in glycosylation, this lectin domain was shown to preferentially bind N-glycans without alpha2,3-sialylation. Since proximal promoter sequences were delineated to diverge markedly among galectin genes and resulting differences in expression profiles were exemplarily documented immunohistochemically, the intrafamily diversification appears to have assigned this protein to a characteristic expression and activity profile among galectins. Our data thus take the crystallographic information to the level of the lectin in solution and in tissues by a strategic combination of spectroscopic and cell/histochemical assays.

PubMed: 20227520
DOI: 10.1016/j.biocel.2010.03.007

実験手法

X-RAY DIFFRACTION (2.03 Å)