LECTINS

• Multivalent carbohydrate-binding proteins or glycoproteins, not enzymes or antibodies – old concept  new concept - proteins which specifically bind CHO

Gal-binding, soluble, metal-independent, no disulfide bridges, no sugar chains, no signal sequences, acetylated; for cellular development and differentiation, morphogenesis,
Galectins
tumor metastasis, apoptosis, RNA splicing; Hemagglutinin – binds RBC, 1st galectin discovered, 14-16kDa, electric organ of electric eel, similar to β-galactoside
Proto binds same CHO
Chimera Binds CHO and non-CHO
Tandem binds 2 distinct CHO
C-type Ca2+ dependent, CHO binding, lectin domain structural maintenance, molecular organization of CRDs, CRD-dependent activity
Soluble attached, single lectin domain, domain between 2 tandem
Lecticans not well-characterized, has CRD near C-terminus; versican, aggrecan, neurocan, brevican
flower-bouquet, collagen-like (Gly-X-Y), host defense w/o antibody involvement, N-terminus collagen domain, C-terminus C-type lectin domain, Chr10q22-23
• Subunit polypeptide x 3 = helix x 6 = MBP (complement activation via lectin pathway);
• helix x 4 = BKG (X-like, opsonization, anti-HIV and influenza)
Collectins
• Lectin pathway: MBL-MASP + pathogen  C4 & C2 proteolysis  C4bC2a  C3 cleaving; MASP -1 cleaves C3 and C2, MASP-2 cleaves C4 and C2
• Direct Effect – inhibition of viral attachment, physical removal or inhibit viral growth
• Indirect Effect – virolysis, phagocytosis, cell lysis
Secreted MBL, BKG / conglutinnin, CL-43 (collectin), SP-A (surfactant protein), SP-D
Non-secreted CL-L1 (liver), CL-L2
Membrane CL-P1
Transmembrane bound to plasma membrane, has transmembrane domain
cell-cell adhesion molecules, leukocyte-endothelial cell adhesion, single C-type lectin domain, EGF-like domain, several CRDs, transmembrane domain, shorter cytoplasmic
tail, affinity to oligosaccharides with sialyl-Lex or –Lea = ↑ sialic acid
Selectins • Leukocyte Extravasation = tethering & rolling (rapid, transient binding & dissociation between selectins, leukocyte slows down)  signaling (elaboration of membrane
selectins & platelet activating factors)  adhesion (adhesion of PAF, binding of integrins + CAD or ICAM)  extravasation/diapedesis (squeeze between endothelial
cells)
L (leukocyte) WBC membrane, GlyCAM-1, CD34, Sgp200, MAdCAM-1
E (endothelium) blood vessel endothelium
P (plasma membrane) endothelial side also, PSGL-1
single transmembrane domain, extracellular C-terminus with CRD, cytoplasmic N-terminus, common AA motif for association with clathrin-coated vesicles, oligomerization;
Type II receptors
macrophage Gal/GalNAc specific lectin; low affinity IgE receptor (CD23)
Asialogylcoprotein receptor
molecular uptake into cells through endocytosis
(hepatocytes)
NK cell receptor (NKR-P1) signal transduction based on cell-cell recognition
Type I transmembrane Extracellular N-terminus with tandem CRD, cysteine-rich, Fibronectin Type II domain, transmembrane domain, cytoplasmic C-terminus
proteins • Cell surface mannose receptors (macrophages), DEC-205 (dendritic cell surface), Siglecs
Annexins Ca2+ and phospholipids binding proteins, 30-40kDa, diverse N-terminus domain, C-terminus regions: 4 helical domains, binding site, binds PS, PE, PI
II TPA, tenascin
IV binds with Ca2+, sialoglycoproteins, GAGs, kidneys and pancreas, apical sorting vesicles
V collagen, lectin activity, exocrine neurotropic
VI lectin activity
immunoglobulin, sialic acid-binding, origin predates vertebrate emergence, AA conserved in Ig-like domains (Arg in β strand F, 2 aromatics (Phe/Tyr), 3 cysteines, N-terminal V-
I-type / Siglecs
set Ig-like domains, C2-set Ig-like domains, transmembrane domain, cytosolic tail, Gene Chr19q
Original
sialoadhesin tissue macrophages
CD22 B cells
MAG myelinating cells
CD33
CD33 related siglecs innate immunity, granulocytes, monocytes/macrophages