Chemistry Reference
In-Depth Information
receptors. Equally intriguing, dynamic binding-site evolution holds true for other
lectin families such as the galectins or siglecs, fulfi lling the structural prerequisite
for nonredundant activity profi les [2-5]. There are more, not yet structurally well-
defi ned lectin sites, found in the
-
defensins (please see Chapter 26) or the sea urchin 350- kDa sperm - binding
protein and a nucleocytoplasmic GlcNAc-binding protein, the two latter proteins
belonging either to the hsp (heat shock protein) 110 and hsp 70 groups,
respectively.
When looking at the occurrence of folds in plant lectins (Chapter 18), several
motifs are shared among plant and animal lectins such as the
α
M
-integrin (please see also Figure 29.4 ),
α
/
θ
- sandwich fold of
leguminous agglutinins, the classical example being concanavalin A (for illustra-
tion, please see Figure 16.1a), the
β
- trefoil fold (fi rst detected in soybean trypsin
inhibitor) in the lectin subunit of AB-toxins (ricin and others), and in amaranthin
as well as the hevein-like domain in wheat germ agglutinin and also chitinases.
Close inspection of positioning of the binding sites and/or the binding mode
intimates a convergent rather than divergent course of evolution in the mentioned
cases [6]. This aspect should be reckoned with in any future suggestions for a ter-
minology system. With these multiple folds engaged in sugar recognition, the
expectation is nourished for multiple functions.
β
19.2
Functions of Animal and Human Lectins
In concert with the glycans of cellular glycoconjugates, lectins can turn their car-
bohydrate - binding activity into specifi c recognition already in the endoplasmic
reticulum and then at the cell surface. As already noted in Chapter 6, the nascent
and processed
N
-glycans, originating from the precursor common to all Asn- X -
Ser/Thr - defi ned acceptor sites, are signals for quality control by virtue of their
ligand capacity. The information at each stage of glycan processing is translated
by lectins into effi cient monitoring for correct folding of nascent glycoproteins and
into ensuing intracellular transport. This intracellular activity profi le fi lls the fi rst
part of Table 19.2. Of note, the glycans added in a cotranslational manner may
well guide folding pathways and later infl uence secretory effi ciency and protein
activity/stability, these processes in principle also involving intramolecular
protein-carbohydrate interactions or a switching-off of intermolecular interac-
tions. When glycoproteins with mature glycans fi nally reach the cell surface, cell
adhesion and diverse cellular responses can be attributed to
cis/trans
interactions
(Table 19.2). Examples for lectin-elicited intracellular signaling routes leading to
responses such as growth control are further explained with illustrations in Chap-
ters 25 and 27 (Figures 25.3 and 27.2 ).
Toward these ends, a factor different from domain folding comes into play. In
addition to direct ligand binding by a lectin' s carbohydrate recognition domain
(CRD), spatial aspects of CRD arrangement contribute markedly to
in vivo
lectin
functionality. They not only increase the affi nity by multivalent interactions but
