期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 292, 期 43, 页码 17845-17856出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M117.802793
关键词
-
资金
- Ministry of Science and Technology of Taiwan [104-2113-M-010-001-MY2, 106-2113-M-010-005-MY2, 106-2321-B-001-042]
Galectins are a family of lectins that bind beta-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 selfassociation- related multivalency of galectin-3 at the residuespecific level. We show that the disordered N-terminal domain (residues similar to 20-100) interacts with itself and with a part of the CRD not involved in carbohydrate recognition (beta-strands 7-9; residues similar to 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.
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