Dépôt numérique

Homodimer Interface Mutations of Human Galectin-7 alter Its Biological Activity

Pham, Ngoc Thu Hang, Létourneau, Myriam, Fortier, Marlène, Hernandez, Carolina Perusquía, Pinoteau, Marie-Aude, Gagnon, Jacinthe, Egesborg, Philippe, Chatenet, David, St-Pierre, Yves ORCID: https://orcid.org/0000-0002-1948-2041, Calmettes, Charles et Doucet, Nicolas ORCID: https://orcid.org/0000-0002-1952-9380 (2019). Homodimer Interface Mutations of Human Galectin-7 alter Its Biological Activity In: 33rd Annual Symposium of the Protein-Society, 30-03 June-July 2019, Seattle, Washington.

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Human galectins are beta-galactoside binding proteins subdivided into three groups in accordance with their structural organization: tandem repeat, chimera, and prototype. Among these galectins, prototype galectin-7 (GAL-7), characterized by a homodimeric molecular organization of its carbohydrate recognition domain (CRD), is involved in different types of cancer, including carcinomas, lymphomas and melanomas. Its overexpression in tumor cells not only confers resistance to cell death stimuli, but extracellular GAL-7 also induces apoptosis of lymphocytes, abrogating immune system response against tumor antigens. Consequently, GAL-7 is a promising target for cancer therapy. To this day, the development of GAL-7 modulators has almost exclusively focused on small-molecule Glycan Binding Site (GBS) inhibitors aimed at perturbation of glycoreceptor interactions. However, due to high GBS similarity among different galectin homologs, this remains a high risk strategy because of unwanted offtarget effects on other beneficial anti-tumor galectins. Furthermore, GBS inhibitors are ineffective at targeting glycan-independent function of GAL-7. New approaches are thus required to develop effective and highly specific GAL-7 inhibitors. Prior structural investigations of ancestral galectins have suggested that stabilization of their oligomeric state through evolutionary pressure improves ligand affinity and biological function. Since destabilization of GAL-7 architecture could potentially alter its affinity towards glycoproteins and biological function, our main research objective is to dissect the molecular importance of GAL-7 homodimer formation in celullar function. In this study, we will present the impact of homodimer interface mutations on protein stability and induction of Jurkat T-cell apoptosis.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Protein Science 28(suppl 1): 151 ABS351
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 22 juill. 2021 21:55
Dernière modification: 15 févr. 2022 15:33
URI: https://espace.inrs.ca/id/eprint/11732

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