8HL9

Crystal structure of Galectin-8 C-CRD with part of linker

Summary for 8HL9

• Entry DOI: 10.2210/pdb8hl9/pdb
• Descriptor: Galectin-8 (2 entities in total)
• Functional Keywords: binding sugar, immunological function, linker, sugar binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 16713.10

Authors

Si, Y.L. (deposition date: 2022-11-29, release date: 2023-07-05, Last modification date: 2024-05-29)

Primary citation

Si, Y.,Cai, J.,Zhu, J.,Wang, Y.,Zhang, F.,Meng, L.,Huang, J.,Shi, A.
Linker remodels human Galectin-8 structure and regulates its hemagglutination and pro-apoptotic activity.
Int.J.Biol.Macromol., 245:125456-125456, 2023

PubMed Abstract: 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.

PubMed: 37331541
DOI: 10.1016/j.ijbiomac.2023.125456

Experimental method

X-RAY DIFFRACTION (1.6 Å)