F-Type Lectins: A Highly Diversified Family of Fucose-Binding Proteins with a Unique Sequence Motif and Structural Fold, Involved in Self/Non-Self-Recognition

Abstract

The F-type lectin (FTL) family is one of the most recent to be identified and structurally characterized. Members of the FTL family are characterized by a fucose recognition domain [F-type lectin domain (FTLD)] that displays a novel jellyroll fold (“F-type” fold) and unique carbohydrate- and calcium-binding sequence motifs. This novel lectin family comprises widely distributed proteins exhibiting single, double, or greater multiples of the FTLD, either tandemly arrayed or combined with other structurally and functionally distinct domains, yielding lectin subunits of pleiotropic properties even within a single species. Furthermore, the extraordinary variability of FTL sequences (isoforms) that are expressed in a single individual has revealed genetic mechanisms of diversification in ligand recognition that are unique to FTLs. Functions of FTLs in self/non-self-recognition include innate immunity, fertilization, microbial adhesion, and pathogenesis, among others. In addition, although the F-type fold is distinctive for FTLs, a structure-based search revealed apparently unrelated proteins with minor sequence similarity to FTLs that displayed the FTLD fold. In general, the phylogenetic analysis of FTLD sequences from viruses to mammals reveals clades that are consistent with the currently accepted taxonomy of extant species. However, the surprisingly discontinuous distribution of FTLDs within each taxonomic category suggests not only an extensive structural/functional diversification of the FTLs along evolutionary lineages but also that this intriguing lectin family has been subject to frequent gene duplication, secondary loss, lateral transfer, and functional co-option.

An F-type lectin domain directs the activity of Streptosporangium roseum alpha-l-fucosidase

“…F-type lectins are fucose-binding lectins with L-fucose (HX(26) RXDX(4)R/K) and calcium-binding sequence motifs and an F-type lectin fold (Bianchet et al 2002). They are phylogenetically widespread but selectively distributed in viruses, bacteria and eukaryotes (Bishnoi et al 2015), and have diverse functions ranging from innate immunity in fishes and amphibians to protoplast regeneration in the green alga, Bryopsis plumosa and virulence in the bacteria, Streptococcus pneumoniae and Streptococcus mitis (Vasta et al 2017). Several eukaryotic F-type lectins (e.g., Anguilla anguilla agglutinin (AAA), Morone saxatilis agglutinin (MSA)) (Bianchet et al 2002(Bianchet et al , 2010 and the F-type lectin domains (FLDs) of a couple of bacterial proteins (Streptococcus pneumoniae SP2159 and Streptococcus mitis lectinolysin) (Boraston et al 2006;Farrand et al 2008;Feil et al 2012) have been biochemically and structurally characterized.…”

Proteome-wide prediction of bacterial carbohydrate-binding proteins as a tool for understanding commensal and pathogen colonisation of the vaginal microbiome

“…The second domain of interest is CBM47, shown to be fucose-specific in the lectin regulatory domain of a cholesterol-dependent cytolysin present in some S. mitis strains (Feil, Lawrence et al 2012). It shares structure and sequence similarity with the F-lectins from fishes (Vasta et al, 2017). In our study, this fucose-binding module is identified in S. mitis as well as in some pathobionts, i.e.…”

LectomeXplore, an update of UniLectin for the discovery of carbohydrate-binding proteins based on a new lectin classification

“…In order to characterise conserved motifs in lectin sequences, a new classification that accounts for different levels of sequence similarity, was needed. We ruled out using taxonomy as a classification criterion since low sequence similarity exists in some lectin families across kingdoms, such as the F-type lectins that are conserved from bacteria to mammals ( 26 ). In contrast, folds are more conserved than sequences and offer a more relevant criterion for building a classification.…”