Evolutionary analysis reveals collective properties and specificity in the C‐type lectin and lectin‐like domain superfamily

Abstract

Members of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily share a common fold and are involved in a variety of functions, such as generalized defense mechanisms against foreign agents, discrimination between healthy and pathogen-infected cells, and endocytosis and blood coagulation. In this work we used ConSurf, a computer program recently developed in our lab, to perform an evolutionary analysis of this superfamily in order to further identify characteristics of all or part of its members. Given a set of homologous proteins in the form of multiple sequence alignment (MSA) and an inferred phylogenetic tree, ConSurf calculates the conservation score in every alignment position, taking into account the relationships between the sequences and the physicochemical similarity between the amino acids. The scores are then color-coded onto the three-dimensional structure of one of the homologous proteins. We provide here and at http://ashtoret.tau.ac.il/ approximately sharon a detailed analysis of the conservation pattern obtained for the entire superfamily and for two subgroups of proteins: (a) 21 CTLs and (b) 11 heterodimeric CTLD toxins. We show that, in general, proteins of the superfamily have one face that is constructed mostly of conserved residues and another that is not, and we suggest that the former face is involved in binding to other proteins or domains. In the CTLs examined we detected a region of highly conserved residues, corresponding to the known calcium- and carbohydrate-binding site of the family, which is not conserved throughout the entire superfamily, and in the CTLD toxins we found a patch of highly conserved residues, corresponding to the known dimerization region of these proteins. Our analysis also detected patches of conserved residues with yet unknown function(s).

Molecular cloning and characterization of a C-type lectin from Ancylostoma ceylanicum: Evidence for a role in hookworm reproductive physiology

“…CTLs are distinguished from other lectins by structural homology in the carbohydraterecognition domain (CRD), a 115-130 amino acid segment with a conserved spacing and number of cysteine residues, which form disulfide bonds that stabilize a double loop structure [1,2,5]. Using the Conserved Domain Search service (CD-Search) available through the NCBI [35], we confirmed the similarity of AceCTL-1 to other C-type lectins.…”

“…Lectins are single or multi-domained glycoproteins capable of binding sugar moieties through specific interaction with an intramolecular carbohydrate recognition domain (CRD) [1][2][3]. In certain physiologic settings, lectins act as recognition molecules, mediating cell adhesion and signal transduction events following binding to carbohydrates [3,4].…”

“…Lectins have been characterized in a multitude of species, including plants, mammals, viruses, and parasites, with specific functions that vary substantially. The C-type lectins (CTLs) are a diverse subset of lectins that bind carbohydrates in a calcium dependent manner [2,5]. Calcium is not only required for functional binding of CTLs, but also serves to stabilize their molecular structure.…”

Molecular cloning and expression of a C-type lectin gene from Venerupis philippinarum

“…Lectins are a family of single or multidomain glycoproteins capable of binding sugar moieties through specific interaction with an intramolecular carbohydrate recognition domain, CRD [2][3][4], and are considered to be one of the important PRPs [5]. Researches have illustrated that lectins act as recognition molecules, mediating cell adhesion and signal transduction events through binding to carbohydrates [3,6].…”

“…Lectins exist in almost all living organisms and can be divided into seven subgroups according to their structures and functions [7]. The C-type lectin family is one of the major groups that bind carbohydrates in a calcium dependent manner [2,8,9]. All the C-type lectins share the same structural features such as CRD sequences, disulfidebond positions, and calcium binding sites [10].…”