Lectin
Lectins are sugar-binding proteins which are highly specific for their sugar moieties. They typically play a role in biological recognition
phenomena involving cells and proteins. For example, some viruses use lectins
to attach themselves to the cells of the host organism during infection. The
name "lectin" is derived from the Latin word legere, meaning, among other things, "to
select".
Most
lectins are basically non-enzymic in action and non-immune in origin. Lectins
occur ubiquitously in nature. They may bind to a soluble carbohydrate or to a
carbohydrate moiety which is a part of a glycoprotein or glycolipid. They typically agglutinate certain animal cells and/or
precipitate glycoconjugates (Loris et al. 1998).
Lectins
serve many different biological functions in animals, from the regulation of cell adhesion to glycoprotein synthesis and the control of protein levels in the blood.
They may also bind soluble extracellular and intercellular glycoproteins
(Sharon and Liss 2003).
Some
lectins are found on the surface of mammalian liver cells which specifically
recognize galactose residues. It is believed that these
cell-surface receptors are responsible for the removal of certain glycoproteins
from the circulatory system (Sharon and Liss 2003).
Another
lectin is a receptor which recognizes hydrolytic enzymes containing mannose-6-phosphate, and subsequently targets these
proteins for delivery to the lysosomes. I-cell disease is one type of defect in this particular system.
Lectins
are also known to play important roles in the immune system by recognizing carbohydrates that are found exclusively on pathogens, or that are inaccessible on host cells. Examples are the
lectin complement
activation pathway
and Mannose binding
lectin (Sharon
and Liss 2003).
Purified
lectins are important in a clinical setting because they are used for blood typing. Some of the glycolipids and glycoproteins on an
individual's red blood cells can be identified by lectins. A lectin from Dolichos biflorus is used to identify cells that belong to the A1 blood
group. A lectin from Ulex europaeus is used to identify the H blood
group antigen. A lectin from Vicia graminea is used to identify the N blood group antigen.
The Role of Winged Bean Lectin on
Human blood
Recognition
is a key event in many biological phenomena. It is also an initiation step in
numerous processes, based on cell-cell interactions, such as fertilization,
embryogenesis, organ formation, immune and microbial defences, etc.. Carbohydrates
perched at the surface of the cells provide cells with their individuality and recognition
patterns that generally play a crucial role in the day to day life of an
ordinary cell (Sharon and Liss 1989). Aberrant expression of sugars on the
surface of the cell is hallmark of diseases such as autoimmune disorders and
neoplastic transformation (Sharon and Liss 1989).
The
discovery of lectins, a class of multivalent proteins that bind sugars
selectively much as antibodies bind to antigens was a great step in the
elucidation of the mechanism of cellular recognition in general and the role of
sugars therein in particular. Because of their sugar selectivity lectins display
blood group and tumor cell specific agglutination, mitogenicity etc.
Consequently they are used routinely in clinics and blood banks as well as in
the isolation and purification of glycoproteins . As all the activities
of lectins are manifestation of their sugar specificities and as they provide
prototype model systems for the interactions that occur at cell surfaces as
well as protein-sugar interactions, the combining sites of lectins have become
objects of intense scientific scrutiny in our laboratory for the last decade.
Thermodynamic
investigations reported here pertain to the general features of
protein-carbohydrate recognition and more specific ones of Winged bean
(Psophocarpus tetrasonolobus) basic agglutinin (WBAI) which has been shown by
us earlier to interact exquisitely with blood group A-reactive sugars. These
studies by Pury and Surolia (1994) underscore the important part played by
sugars not involved directly in binding in favourably orienting the interacting
regions of sugars and the role of solvent (water) re-organization in these
interactions.
Lemieux
et al. (1993) studied about the
binding of the H-type 2 human blood group determinant by a winged bean (Psophocarpus
tetragonolobus) acidic lectin. Interactions that importantly contribute to
the specificity of the complex formation are provided by CH2-6b, OH-4b, OH-3b,
and OH-2c of 1. On the basis of the relative activities of the monodeoxy and mono-0-methyl
derivatives of 1, the hydroxyl groups at the 3a, 6a, and 4c positions
become located at the periphery of the combining site, whereas the CH30-la,
NHAc-2a, and CH3-5c groups are more remote from the protein surface and fully
exposed to bulk water. Whereas the WBA I1 lectin marginally recognizes the
H-type 1 related trisaccharide (a-L-Fuc-(lc + 2b)-p-~-Gal-(lb +
3a)-P-D-GlcNAc-OMe, 23), the de-N-acetyl derivative (24) is bound 3.4 times
more strongly than 1. This and other results, which are related to changes in
interaction between the ligand and the apron of the combining site, are
attributed to changes in hydration that lead to enthalpy~ntropyc ompensation.
In certain cases, the interactions are found to stabilize the complex.