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

Geoffrey Koh,Dong-Yup Lee,Daren Poh,Kong-Peng Lam,Yujian Yao,Say Kong Ng,Ariana Low,Vincent Vagenende,Victor Vai Tak Wong

doi:10.1186/1471-2105-12-s14-s5

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.

Highlights

Introduction to methology and encoding rulesJournal of Chemical Information and Computer Sciences 1988, 28:31-36.30
Van Liempt et al [12] analyzed the molecular structures of the C-type lectins Dendritic cells (DCs)-SIGN and L-SIGN, and identified the residues that were responsible for the differences in their carbohydrate binding profiles
As an initial analysis of the global glycan binding profile of CLEC17A, we looked at the terminating monosaccharides of the dockable glycans: it has been suggested in Taylor and Drickamer [46] that the binding specificities of C-type lectins may be due to their interaction with the terminal sugar

Summary

Introduction

Introduction to methology and encoding rulesJournal of Chemical Information and Computer Sciences 1988, 28:31-36.30. It 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 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. C-type lectins are Ca2+-depending sugar-binding proteins that are involved in several immune-related and other physiological functions. They are ubiquitous in the animal kingdom, and exist mostly as membrane receptors. C-type lectins play an important role in pathogen recognition and cell-cell interaction through specific binding with glycans (sugars) found on the surfaces of target cells and glycosylated molecules [1]. It is imperative to develop techniques in glycoinformatics, so as to aid the elucidation and analysis of protein-glycan interactions - one of the key processes in the mammalian immune system [5]

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Conclusion