Perturbing dimer interactions and allosteric communication modulates the immunosuppressive activity of human galectin-7

Abstract

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Glycomimetics for the inhibition and modulation of lectins

“…Longer-range communication of loops 1, 2 and 5 perturbing protein-protein interaction was suggested from protein engineering and biophysical characterization. 553 3.3.3 C-type lectins. In contrast to the galectins, for CTLs it was already reported prior glycomimetic development that this lectin family harbours intrinsic dynamics in their protein structure.…”

“…Longer-range communication of loops 1, 2 and 5 perturbing protein–protein interaction was suggested from protein engineering and biophysical characterization. 553 …”

Galectin functions in cancer-associated inflammation and thrombosis

“…Recombinant human galectin-7 protein could inhibit apoptosis in Jurkat T cells, indicating on immunosuppressive function (351). This proapoptotic effect was inhibited by targeting the dimer interface of galectin-7, thereby disrupting homodimerization (352). Galectin-7 also regulates immune response to transplantation by promoting Th1/Th2 differentiation toward Th1, which results in increased rejection of grafted hearts (216,353).…”

Early-Onset Parkinson Mutation Remodels Monomer–Fibril Interactions to Allosterically Amplify Synuclein’s Amyloid Cascade

“…In its monomeric form, αS is an intrinsically disordered protein (IDP) that samples a wide range of dynamic conformations, including both “closed” and “open” states (Figure B). − Closed conformers are stabilized by electrostatic interactions between the positively and negatively charged αS N- and C-termini (NTR and CTR), respectively, which occlude the aggregation-prone and fibrillization-essential non-amyloid-β component (NAC) region (Figure A, B). In the open conformers, the NAC segment is exposed and available to self-associate into oligomers and fibrils (Figure A, B). ,, Once formed, wild-type (wt) αS fibrils recruit additional monomers primarily through electrostatic interactions between the fibril C-terminus and the monomer N-terminus, driving closed-to-open monomer transitions and promoting secondary nucleation and further elongation of αS fibrils. − Understanding how PD-related mutations alter these self-association equilibria from monomer to fibrils (Figure B) is essential to understanding the molecular etiology of PD and possibly other amyloid-driven dementias. − …”

“… 14 , 15 , 23 Once formed, wild-type (wt) αS fibrils recruit additional monomers primarily through electrostatic interactions between the fibril C-terminus and the monomer N-terminus, driving closed-to-open monomer transitions and promoting secondary nucleation and further elongation of αS fibrils. 24 − 31 Understanding how PD-related mutations alter these self-association equilibria from monomer to fibrils ( Figure 1 B) is essential to understanding the molecular etiology of PD and possibly other amyloid-driven dementias. 32 − 34 …”