%0 Journal Article
%T Linker remodels human Galectin-8 structure and regulates its hemagglutination and pro-apoptotic activity.
%A Si Y
%A Cai J
%A Zhu J
%A Wang Y
%A Zhang F
%A Meng L
%A Huang J
%A Shi A
%J Int J Biol Macromol
%V 245
%N 0
%D 2023 Aug 1
%M 37331541
%F 8.025
%R 10.1016/j.ijbiomac.2023.125456
%X Numerous articles have reported the involvement of linker in regulating bioactivity of tandem-repeat galectins. We hypothesize that linker interacts with N/C-CRDs to regulate the bioactivity of tandem-repeat galectins. To further investigate structural molecular mechanism of linker in regulating bioactivity of Gal-8, Gal-8LC was crystallized. Gal-8LC structure revealed formation of β-strand S1 by Asn174 to Pro176 from linker. S1-strand interacts with C-terminal of C-CRD via hydrogen bond interactions, mutually influencing their spatial structures. Our Gal-8 NL structure have demonstrated that linker region from Ser154 to Gln158 interacts with the N-terminal of Gal-8. Ser154 to Gln158 and Asn174 to Pro176 are likely involved in regulation of Gal-8's biological activity. Our preliminary experiment results revealed different hemagglutination and pro-apoptotic activities between full-length and truncated forms of Gal-8, indicating involvement of linker in regulating these activities. We generated several mutant and truncated forms of Gal-8 (Gal-8 M3, Gal-8 M5, Gal-8TL1, Gal-8TL2, Gal-8LC-M3 and Gal-8_177-317). Ser154 to Gln158 and Asn174 to Pro176 were found to be involved in regulating hemagglutination and pro-apoptotic activities of Gal-8. Ser154 to Gln158 and Asn174 to Pro176 are critical functional regulatory regions within linker. Our study holds significant importance in providing a profound understanding of how linker regulates biological activity of Gal-8.