Introduction to "Lectin"

Jun Hirabayashi (Teikyo University, Faculty of Pharmaceutical Sciences)
 What is lectin? According to an old definition,"Lectins are multivalent carbohydrate-binding proteins or glycoproteins except for enzymes and antibodies." Such a narrow definition, however, seems no longer relevant, because a significant number of exceptions are evident now. For today, a more flexible interpretation would be accepted, e.g., "lectins are simply defined as proteins which specifically bind (or crosslink) carbohydrates." As exceptions, ricin, the oldest lectin, is actually the enzyme RNA-N-glycosidase, Charcot-Leyden crystal protein (galectin-10) is known as lysophospholipase, and I-type lectins such as sialoadhesin are members of the immunoglobulin superfamily. Multivalency may not be an absolute requirement, even though it is still an important factor for most lectins. Since lectins generally have no apparent catalytic activity like enzymes, their physiological functions remain unclear. Unfortunately, for this reason, the term "lectin" has sometimes been used as a convenient taxon to "group out" carbohydrate-binding proteins, the functions of which were unknown. At present, however, probably no one will oppose the idea that lectins are "deciphers of glycocode".

Lectins are often classified based on saccharide-specificity. Though this conventional method is familiar and practically useful, it is not necessarily relevant for refined specificity. Lectins in the same category (e.g., galactose-specific lectins) show considerably different sugar-binding preferences. Moreover, an increasing number of lectins which never show high affinity to simple saccharides have been found.

Classification is a natural human activity. It is after all a convenient means to classify an incomplete set of data each time. From the standpoint of modern molecular biology, lectins should be understood under the concept of protein family. By this criterion, we can judge objectively evolutionary kinship between lectins. In other words, lectins whose structures have been determined are "registered." Of course, still many lectins remain orphans, having no homologous proteins at the moment. However, as genome projects of various organisms, including humans, are in rapid progress, classification of lectins, first of all, under the concept of protein (gene) families seems most relevant.

To start this GlycoWord, I have chosen a few representative lectin families. For each family or subfamily, a brief explanation will be made by an authority on that field. The following is an introduction to the contents of a "Lectin Section" to be started soon.
1) Galectins are a rapidly growing family of animal lectins. All of them share galactose-specificity.
2) Ca-dependent (C-type) animal lectins form an extremely large family, composed of members having diverse structures and functions.
3) Among this C-type lectin family, selectins form a distinguished subfamily by their specific function in leukocyte adhesion to endothelial cells through sialyl-LewisX recognition.
4) Collectins, another subfamily of C-type lectins specific for mannose, have a unique structure consisting of a C-type lectin domain and a collagen-like domain. They are supposed to be involved in innate immunity.
5) On the other hand, invertebrates are known to contain various lectins in their body fluids, probably as body-protection factors. Japanese groups have been making significant contributions to this field. Recently, some lectins from an echinoderm were found to show hemolytic activity.
6) Annexins are a group of proteins having affinity to lipids, but recently they proved to be lectins showing a certain binding activity to glycosaminoglycans. Much attention has been paid to their functions as lectins. All of the above are of animal origin, but there are many unique lectins in the plant kingdom, too.
7) The legume lectin family consists of a large number of members, such as ConA, with variable saccharide specificity comparable to C-type lectins. Recently, mechanistic studies have been made on how such specificities and affinities are controlled.
8) Ricin was the first lectin investigated in Russia more than 100 years ago. It is now evident that ricin has many other homologous members which differ in either toxicity or sugar-binding specificities.
Nevertheless, the above approach is not enough to understand what lectins are: even though members of the same families are similar, it does not necessarily mean they are the same (usually they have some "personality"). The matter of "species specificity" is also involved. Once we get a grasp on both the general and specific aspects of the lectins, we will come closer to understanding the essence of carbohydrates and life.
Dec.15, 1997

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