Differentiation of L-Type Lectin Domains into Two Directions

 More than one hundred leguminous lectins have been isolated from the seeds of leguminosae plants and are widely used as tools for purification and identification of specific glycoproteins. cDNA cloning, amino acid sequence analyses, and X-ray crystallographic analyses of these lectins demonstrate that these proteins consist of a large family of leguminous lectins based on structural molecular characteristics and also on the function concerning self-defense against fungi and viruses by aggregating these organisms (see GlycoWord LE-A03).

It was recently reported that another kind of protein having structural homology with these plant leguminous lectins was also present in animal cells (1), and these proteins were classified as L-type lectins. Cargo receptors having an L-type lectin domain at a lumenal part of their molecules transport newly synthesized glycoproteins from the ER through the Golgi to the cell surfaces. Four members of these receptors are reported; ERGIC-53, which has been identified as a marker of ER and Golgi intermediate compartment, VIP36, which has been purified from detergent-insoluble membrane fraction, and their homologues ERGL and VIPL, respectively. Although both amino acid residues participating with sugar- and metal-binding and three-dimensional structures of these proteins are highly conserved among plant leguminous lectins and cargo receptors, several different characteristics have been clarified between leguminous lectins and cargo receptors. In the case of cargo receptors, the catch/release mechanism of sugars is essential for vectorial transport of cargo proteins in the cells.
Fig.1Regulation of sugar-binding activities of cargo receptors, ERGIC-53 and VIP36
The sugar-binding activity of ERGIC-53 is enhanced by binding with MCFD2 whereas the activity of VIP36 is increased under acidic pH condition by the association of VIP36 with each other.

ERGIC-53 can bind to sugars when it interacts with MCFD2 (2). VIP36 associates with each other at acidic pH condition and enhances avidity for sugar chains attached to cargo proteins (3) (Fig. 1). Regulation of sugar-binding activities of cargo receptors is important for determining the direction of transport of cargo proteins. In contrast, plant leguminous lectins have no release mechanism of ligands, indicating that these lectins are suitable for aggregating fungi or viruses to interfere their growth. L-type lectin domains have evolved in two different directions and function as self-defense molecules in plant seeds and transport receptors in the cells (Fig. 2).
Fig.2 Possible model for evolution of L-type lectin domains
Plant leguminous lectins acquired the region which produces homotetramers stably. Cargo receptors have not only a stalk domain, transmembrane domain, and cytoplasmic domain but also a regulating region for sugar-binding activity in their molecules.

Kazuo Yamamoto (Graduate School of Frontier Sciences, The University of Tokyo)
References (1) Fiedler K, Simons K: A putative novel class of animal lectins in the secretory pathway homologous to leguminous lectins. Cell, 77, 625-626, 1994
(2) Zhang B, Cunningham MA, Nichols WC, Bernat JA, Seligsohn U, Pipe SW, McVey JH, Schulte-Overberg U, de Bosch NB, Ruiz-Saez A, White GC, Tuddenham EG, Kaufman RJ, Ginsburg D : Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nature Genet. 34, 220-225, 2003
(3) Yamamoto, K. Intracellular transport and sorting of glycoproteins by cargo receptors. Seikagaku (in Japanese) 76, pp240-255, 2004
Jun. 30, 2005

GlycoscienceNow INDEX gbvy[Wز֭