Animal and Human Lectins - The Sugar Code - page 327

growth inhibition in activated T cells or in neuroblastoma cells (please see Chapters
25 and 27 for details) [4]. This principle fi gures as a decisive driving force not only
for galectins, but also for other lectins such as selectins (Table 19.2). As further
example, intercellular contacts via the dendritic cell lectin DC - SIGN ( d endritic c ell -
s pecifi c I CAM - 3 g rabbing n onintegrin) similarly hinge on a cell- type - specifi c selec-
tion of the target glycoprotein. The dendritic cell engages the lectin to bind glycans
of intercellular adhesion molecule ( ICAM ) - 2 on endothelial cells, of ICAM - 3 on T
cells and of the 2 - integrin) on

neutrophils and of various pathogens with clustered Man or Lewis epitopes [11] .
In addition to glycans, the two galectins, as noted above for the C-type lectin-like
NK cell receptors or hyalectans/lecticans (please see legend to Figure 19.1 ), also
bind peptide motifs. This property facilitates intracellular functions in pre- mRNA
splicing, placement of oncogenic ras or apoptosis regulation (Table 19.3 ) [4] . Overall,
the details emerging teach the following salient lesson: despite the abundance of
glycan chains on the cell surface, animal and human lectins have a preference for
particular binding partners in a distinct context.
In this sense, shifts in the assembly line for glycans and their substitution
pattern can have an impact on affi nity toward lectins - not only the presence of a
certain epitope counts, but also its topological aspects, starting with the conforma-
tion of the lectin-binding determinant and the complete structure of the glycan
chain including branching and core substitutions. These parameters have a bearing
on lectin binding, although they are not physically involved in the molecular ren-
dezvous [12,13]. It is therefore imperative to systematically profi le factors with
likely bearing on affi nity regulation. If moving in a stepwise manner from the
smallest interaction partner of a lectin, a monosaccharide, to the level of microdo-
mains in membranes, six different layers with regulatory potential are then identi-
fi ed (Table 19.4). They give reason to imply an exquisitely tuned interplay between
structural glycan tailoring and lectin expression, for example in fertilization
(Chapter 24), malignancy (Chapter 25), infl ammation (Chapter 27) or immune
regulation (Info Box 1 in Chapter 30 ).

α M - subunit of the Mac -1 antigen (CR3 receptor, α M β

19.4
Conclusions

The assumption that lectin-carbohydrate recognition is a common mode for inter-
molecular association and biological information transfer is convincingly backed
by the large number of folds with lectin activity. Ensuing intrafamily diversifi cation
within more than a dozen folds with identifi ed CRDs led to a toolbox of specialized
effectors and a broad range of covered functions. Toward this end, covalent and
noncovalent CRD clustering opened the way to optimize ligand selection and to
distinguish glycosignatures. With lectins thus being also sensors of topological
aspects, the affi nity of the binding process can swiftly be regulated by altering the
local density at the level of individual glycoconjugates and even cell surfaces.
Picking functional ligands from the glycomic complexity thus includes context-
dependent parameters, making cell specifi city of lectin binding possible.