The intrinsically disordered N-terminal domain of galectin-3 dynamically mediates multisite self-association of the protein through fuzzy interactions.

Autor:	Lin YH; From the Institute of Biochemistry and Molecular Biology and., Qiu DC; From the Institute of Biochemistry and Molecular Biology and., Chang WH; From the Institute of Biochemistry and Molecular Biology and., Yeh YQ; the National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan., Jeng US; the National Synchrotron Radiation Research Center, Hsinchu 30076, Taiwan.; the Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, and., Liu FT; the Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan., Huang JR; From the Institute of Biochemistry and Molecular Biology and jierongh@ym.edu.tw.; the Institute of Biomedical Informatics, National Yang-Ming University, Number 155 Section 2 Li-nong Street, Taipei 11221, Taiwan.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2017 Oct 27; Vol. 292 (43), pp. 17845-17856. Date of Electronic Publication: 2017 Sep 11.
DOI:	10.1074/jbc.M117.802793
Abstrakt:	Galectins are a family of lectins that bind β-galactosides through their conserved carbohydrate recognition domain (CRD) and can induce aggregation with glycoproteins or glycolipids on the cell surface and thereby regulate cell activation, migration, adhesion, and signaling. Galectin-3 has an intrinsically disordered N-terminal domain and a canonical CRD. Unlike the other 14 known galectins in mammalian cells, which have dimeric or tandem-repeated CRDs enabling multivalency for various functions, galectin-3 is monomeric, and its functional multivalency therefore is somewhat of a mystery. Here, we used NMR spectroscopy, mutagenesis, small-angle X-ray scattering, and computational modeling to study the self-association-related multivalency of galectin-3 at the residue-specific level. We show that the disordered N-terminal domain (residues ∼20-100) interacts with itself and with a part of the CRD not involved in carbohydrate recognition (β-strands 7-9; residues ∼200-220), forming a fuzzy complex via inter- and intramolecular interactions, mainly through hydrophobicity. These fuzzy interactions are characteristic of intrinsically disordered proteins to achieve liquid-liquid phase separation, and we demonstrated that galectin-3 can also undergo liquid-liquid phase separation. We propose that galectin-3 may achieve multivalency through this multisite self-association mechanism facilitated by fuzzy interactions. (© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.)
Databáze:	MEDLINE
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