Animal and Human Lectins - The Sugar Code - page 325

Figure 19.1 Illustration of the strategic ways how CRDs in animal lectins are positioned to reach optimal ligand selection (for example to separate self from
nonself-glycan profi les in innate immunity) and topological complementarity. From left to right, the CRD display in the three subtypes within the galectin family
(chimeric, proto-type and tandem-repeat-type arrangements binding to a ganglioside or a branched complex-type N -glycan without or with terminal α 2,3 -
sialylation), the presentation of CRDs (C-type or fi brinogen-like domain) in serum and surfactant collectins or fi colins connected to their collagenous stalks and
the noncovalent association of binding sites in transmembrane C-type lectins by α - helical coiled -coil stalks (for example asialoglycoprotein and Kupffer cell recep-
tors, the scavenger receptor C-type lectin, CD23, DC-SIGN or DC-SIGNR) are given. Similar to tandem-repeat-type galectins the C-type family of lectins also has
a branch of members with this design, that is, immulectins-1, -2 and -3. Next, the tandem-repeat display in the mannose-specifi c macrophage receptor (also
found on dendritic cells, hepatic endothelial cells, kidney mesangial cells, retinal pigment epithelial cells and tracheal smooth muscle cells) and the related C- type
lectin Endo180 with eight domains as well as in the cation-independent P-type lectin with 15 domains is presented. Capacity for sugar binding is confi ned to only
a few domains as depicted. The occurrence of lectin activity for GalNAc- 4 - SO 4 -bearing pituitary glycoprotein hormones in the cysteine-rich domain, a member of
the β -trefoil fold family with one (QxW) 3 domain in the N -terminal section of the macrophage mannose receptor (amino acids 8-128), which is linked via a fi bro-
nectin-type-II-repeat-containing module to the tandem-repeat section, is also included into the schematic drawing for these lectins with more than one type of
CRD per protein chain. Moving further to the right side, the association of a distal CRD in selectins (attached to an epidermal - growth - factor (EGF) - like domain
and two to nine complement-binding consensus repeats) or in the siglec subfamily of I-type lectins using 1-16 C2-set immunoglobulin-like units as spacer
equivalents to let the CRD reach out to contact ligands and to modulate capacity to serve in cis - or trans -interactions on the cell surface is shown. The force-
dependent alterations of the topological arrangement of the two distal domains in selectins accounts for catch bonds of selectins (please see text). A canonical
immunoreceptor tyrosine-based inhibitory motif (ITIM) together with a putative tyrosine-based signaling motif is frequently present in the intracellular portion
of siglecs, especially in the CD33(siglec- 3) - related subgroup. C2 -Set domains linked to fi bronectin-type-III repeats establish the extracellular section of the I-type
lectins L1 and neural cell adhesion molecule (N-CAM). In the matrix, the modular proteoglycans (hyalectans/lecticans: aggrecan, brevican, neurocan and versican)
interact (i) with hyaluronan (and also link protein) via the link-protein-type modules of the N - terminal G1 domain (and an immunoglobulin - like module), (ii) with
receptors binding to the glycosaminoglycan chains in the central region and (iii) with carbohydrates or proteins (fi bulins-1 and -2 and tenascin-R) via the C-type
lectin - like domain fl anked by EGF-like and complement-binding consensus repeat modules (kindly provided by H. Kaltner).