Journal ArticleDOI
Self-association of the galectin-9 C-terminal domain via the opposite surface of the sugar-binding site
Yasuhiro Nonaka,Takashi Ogawa,Souichi Oomizu,Shin-ichi Nakakita,Nozomu Nishi,Shigehiro Kamitori,Mitsuomi Hirashima,Takanori Nakamura +7 more
Reads0
Chats0
TLDR
The high pro-apoptotic activity of G9CCRD seems to be due to the ability to form an oligomer, and 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.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.read more
Citations
More filters
Journal ArticleDOI
Galectin-9 controls the therapeutic activity of 4-1BB–targeting antibodies
Shravan Madireddi,So-Young Eun,Seung-Woo Lee,Ivana Nemčovičová,Amit Mehta,Dirk M. Zajonc,Nozomu Nishi,Toshiro Niki,Mitsuomi Hirashima,Michael Croft +9 more
TL;DR: Agonistic anti–4-1BB suppresses autoimmune and allergic inflammation via binding to Galectin-9, which facilitates 4-1 BB aggregation, signaling, and functional activity.
Journal ArticleDOI
Galectin-9: From cell biology to complex disease dynamics
Sebastian John,Rashmi Mishra +1 more
TL;DR: The latest knowledge on the structure, receptors, cellular targets, trafficking pathways and functional properties of galectin-9 are summarized and how galectIn-9-mediated signalling cascades can be exploited in cancers and immunotherapies are discussed.
Journal ArticleDOI
Regulatory T Cell-Mediated Suppression of Inflammation Induced by DR3 Signaling Is Dependent on Galectin-9.
Shravan Madireddi,So-Young Eun,Amit Mehta,Aruna Birta,Dirk M. Zajonc,Dirk M. Zajonc,Toshiro Niki,Mitsuomi Hirashima,Eckhard R. Podack,Taylor H. Schreiber,Michael Croft,Michael Croft +11 more
TL;DR: A novel function of Galectin-9 is demonstrated in facilitating activity of DR3 related to Treg-mediated suppression, and this protective effect was lost in GalectIn-9−/− mice in a model of experimental autoimmune encephalomyelitis.
Journal ArticleDOI
Crystallization of Galectin-8 Linker Reveals Intricate Relationship between the N-terminal Tail and the Linker.
TL;DR: Galectin-8 (Gal-8) contains two carbohydrate recognition domains (CRD) connected by a peptide linker and observation of two Gal-8 N-terminal CRD structures implies that the N-Terminal tail and the linker may influence each other’s conformation.
Journal ArticleDOI
Characterization of neutralizing antibodies reacting with the 213-224 amino-acid segment of human galectin-9.
Claire Lhuillier,Clément Barjon,Valentin Baloche,Valentin Baloche,Toshiro Niki,Aurore Gelin,Aurore Gelin,Rami Mustapha,Laetitia Claër,Sylviane Hoos,Yoichi Chiba,Masaki Ueno,Mitsuomi Hirashima,Ming Wei,Olivier Moralès,Bertrand Raynal,Nadira Delhem,Olivier Dellis,Philippe Busson,Philippe Busson +19 more
TL;DR: A protective effect of Gal-Nab1 and Gal-nab2 on the apoptotic cell death induced by gal-9 in primary T cells is reported, and cross-species recognition will be an advantage for their assessment in pre-clinical tumor models.
References
More filters
Journal ArticleDOI
NMRPipe: a multidimensional spectral processing system based on UNIX pipes
TL;DR: The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks.
Book ChapterDOI
Protein identification and analysis tools in the ExPASy server
Marc R. Wilkins,Elisabeth Gasteiger,Amos Marc Bairoch,Jean Emmanuel Sanchez,Keith L. Williams,Ron D. Appel,Denis Hochstrasser +6 more
TL;DR: Details are given about protein identification and analysis software that is available through the ExPASy World Wide Web server and the extensive annotation available in the Swiss-Prot database is used.
Journal ArticleDOI
Calculation of protein extinction coefficients from amino acid sequence data
Stanley C. Gill,P H von Hippel +1 more
TL;DR: In this article, a method for calculating accurate molar extinction coefficients for proteins at 280 nm, simply from knowledge of the amino acid composition, was presented, and the method was calibrated against 18 "normal" globular proteins.
Journal ArticleDOI
Protein backbone angle restraints from searching a database for chemical shift and sequence homology
TL;DR: TALOS yields the 10 triplets which have the closest similarity in secondary chemical shift and amino acid sequence to those of the query sequence, and these averages can reliably be used as angular restraints for the protein whose structure is being studied.
Journal ArticleDOI
TALOS+: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts.
TL;DR: Extension of the original 20-protein database to 200 proteins increased the fraction of residues for which backbone angles could be predicted from 65 to 74%, while reducing the error rate from 3 to 2.5%, and addition of a two-layer neural network filter to the database fragment selection process forms the basis for a new program, TALOS+, which further enhances the prediction rate to 88.5%.