Integrative analysis workflow for the structural and functional classification of C-type lectins

Abstract

BackgroundIt is important to understand the roles of C-type lectins in the immune system due to their ubiquity and diverse range of functions in animal cells. It has been observed that currently confirmed C-type lectins share a highly conserved domain known as the C-type carbohydrate recognition domain (CRD). Using the sequence profile of the CRD, an increasing number of putative C-type lectins have been identified. Hence, it is highly needed to develop a systematic framework that enables us to elucidate their carbohydrate (glycan) recognition function, and discover their physiological and pathological roles.ResultsPresented herein is an integrated workflow for characterizing the sequence and structural features of novel C-type lectins. Our workflow utilizes web-based queries and available software suites to annotate features that can be found on the C-type lectin, given its amino acid sequence. At the same time, it incorporates modeling and analysis of glycans - a major class of ligands that interact with C-type lectins. Thereafter, the results are analyzed together with context-specific knowledge to filter off unlikely predictions. This allows researchers to design their subsequent experiments to confirm the functions of the C-type lectins in a systematic manner.ConclusionsThe efficacy and usefulness of our proposed immunoinformatics workflow was demonstrated by applying our integrated workflow to a novel C-type lectin -CLEC17A - and we report some of its possible functions that warrants further validation through wet-lab experiments.

Proteomic analysis unveils a FANCA-modulated neddylation pathway involved in CXCR5 membrane targeting and cell mobility

“…1B). Only one polypeptide belonging to the uncharacterized transmembrane glycan-binding receptor on dividing B cells -C-type lectin domain family 17, member A isoform 1 (CLEC17A or prolectin) protein (Koh et al, 2011) -exhibited a fold change that was similar to the values obtained for FANCD2 and FANCI.…”

Eutirucallin: A Lectin with Antitumor and Antimicrobial Properties

“…Interestingly the Eutirucallin treatment did not affect the viability of fibroblast and macrophage cells but did affect the viability of all tumorigenic cells lines. A previous study indicated that lectins selectively bind to malignant cells because they only bind to specific carbohydrates by recognizing domains present in cell membranes that are differentially expressed in non-tumor cells (Sharon, 2007 ; Sabova et al, 2010 ; Koh et al, 2011 ; Nolte et al, 2012 ). The internalization of lectin improves its intracellular availability and activity (Lichtenstein and Rabinovich, 2013 ).…”