Comparative study of the glycan specificities of cell-bound human tandem-repeat-type galectin-4, -8 and -9статья
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Дата последнего поиска статьи во внешних источниках: 17 мая 2016 г.
Аннотация:Adhesion/growth-regulatory galectins (gals) exert their
functionality by the cis/trans-cross-linking of distinct
glycans after initial one-point binding. In order to define
the specificity of ensuing association events leading to
cross-linking, we recently established a cell-based assay
using fluorescent glycoconjugates as flow cytometry
probes and tested it on two human gals (gal-1 and -3).
Here we present a systematic study of tandem-repeat-type
gal-4, -8 and -9 loaded on Raji cells resulting in the following
key insights: (i) all three gals bound to oligolactosamines;
(ii) binding to ligands with Galβ1-3GlcNAc or
Galβ1-3GalNAc as basic motifs was commonly better than
that to canonical Galβ1-4GlcNAc; (iii) all three gals bound
to 3′-O-sulfated and 3′-sialylated disaccharides mentioned
above better than that to parental neutral forms and (iv)
histo-blood group ABH antigens were the highest affinity
ligands in both the cell and the solid-phase assay. Fine specificity
differences were revealed as follows: (i) gal-8 and
-9, but not gal-4, bound to disaccharide Galβ1-3GlcNAc;
(ii) increase in binding due to negatively charged substituents
was marked only in the case of gal-4 and (iii) gal-4
and -8 bound preferably to histo-blood group A glycans,
whereas gal-9 targeted B-type glycans. Experiments with
single carbohydrate recognition domains (CRDs) of gal-4
showed that the C-CRD preferably bound to ABH
glycans, whereas the N-CRD associated with oligolactosamines.
In summary, the comparative analysis disclosed the
characteristic profiles of glycan reactivity for the accessible
CRD of cell-bound gals. These results indicate the distinct
sets of functionality for these three members of the same
subgroup of human gals.