Playing Modular Puzzle with Adhesion/Growth-Regulatory Galectins: Design and Testing of a Hybrid to Unravel Structure-Activity Relationships
2016
The potent multifunctionality of human galectins is based on their
modular structure in a not yet fully understood manner. A strategy to dissect the
contributions of individual sequence stretches to lectin activity is based on engineering
variants of the natural proteins, which are composed of novel combinations
of distinct parts. On proof-of-principle level, we here describe the design of
a hybrid constituted by the N-terminal tail of chimera-type galectin-3 and the Nterminal
carbohydrate recognition domain of tandem-repeat-type galectin-8, its
production, purification and its serine phosphorylation characteristic for galectin-
3’s tail. As measured for the respective parental proteins, its binding to
(neo)glycoproteins is specific for β-galactosides and inhibitable by lactose, with
KD-value closer to galectin-8 than galectin-3. Cell surface staining indicated similarity of the hybrid’s
reactivity to O-glycans and sensitivity for sialylation to respective properties of tandem-repeattype
galectin-8 and its N-terminal domain. Applied as histochemical tool on tissue sections of murine
jejunum and epididymis, intense lactose-inhibitable signals were recorded intracellularly, with a
distribution profile akin to that of galectin-3. Tested as agglutinin, the hybrid was potent, excelling
wild-type control galectins. The chimera-type design can thus serve as platform for tuning crosslinking
activity.
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