Secondary Sites of the C-type Lectin-Like Fold

Publications: Contribution to journalArticlePeer Reviewed

Abstract

C-type lectins are a large superfamily of proteins involved in a multitude of biological processes. In particular, their involvement in immunity and homeostasis has rendered them attractive targets for diverse therapeutic interventions. They share a characteristic C-type lectin-like domain whose adaptability enables them to bind a broad spectrum of ligands beyond the originally defined canonical Ca2+-dependent carbohydrate binding. Together with variable domain architecture and high-level conformational plasticity, this enables C-type lectins to meet diverse functional demands. Secondary sites provide another layer of regulation and are often intricately linked to functional diversity. Located remote from the canonical primary binding site, secondary sites can accommodate ligands with other physicochemical properties and alter protein dynamics, thus enhancing selectivity and enabling fine-tuning of the biological response. In this review, we outline the structural determinants allowing C-type lectins to perform a large variety of tasks and to accommodate the ligands associated with it. Using the six well-characterized Ca2+-dependent and Ca2+-independent C-type lectin receptors DC-SIGN, langerin, MGL, dectin-1, CLEC-2 and NKG2D as examples, we focus on the characteristics of non-canonical interactions and secondary sites and their potential use in drug discovery endeavors.

Original languageEnglish
Article numbere202400660
Pages (from-to)e202400660
JournalChemistry: A European Journal
Volume30
Issue number30
DOIs
Publication statusPublished - 28 May 2024

Austrian Fields of Science 2012

  • 301207 Pharmaceutical chemistry

Keywords

  • Lectins, C-Type/chemistry
  • Humans
  • Ligands
  • Binding Sites
  • Calcium/metabolism
  • Receptors, Cell Surface/chemistry
  • Cell Adhesion Molecules/chemistry
  • Protein Binding
  • Mannose-Binding Lectins/chemistry
  • Mannose-Binding Lectin/chemistry
  • NK Cell Lectin-Like Receptor Subfamily K/chemistry
  • Antigens, CD/chemistry

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