Glycan Binding Proteins – Diversity, Structure, Recognition Principles and Biology
Lecturers: Kurt Drickamer, Matthew Macauley and Maureen Taylor
OVERVIEW
Glycan-binding receptors are found in all kingdoms of life, but this short course will be focused on mammalian examples, particularly in the immune system. The course is intended as an overview of mammalian glycan-binding receptors, also known as animal lectins. Areas to be covered will include biological functions in the context of cells and organisms as well as biochemical analysis of what sugars are recognized and how specificity is achieved. As galectins will be discussed extensively in a Satellite Meeting, the focus of this course will be on other groups of animal lectins, including the large groups of C-type lectins and siglecs, as well as additional protein families that have been described more recently.
| 13:00-13:05 | Introduction |
| 13:05-13:35 | Maureen Taylor (Imperial College London, UK): Multiple families of animal lectins |
| 13:35-13:45 | Questions/Discussion |
| 13:45-14:15 | Matthew Macauley (University of Alberta, Canada): Siglecs |
| 14:15-14:25 | Questions/Discussion |
| 14:25-14:50 | Kurt Drickamer (Imperial College London, UK): How structure leads to functions of the C-type lectins |
| 14:50-15:00 | Questions/Discussion |
Title: Multiple families of animal lectins
Maureen Taylor
Comparisons across different families of glycan-binding receptors reveals that analogous and often overlapping functions can be performed by proteins that have different types of carbohydrate-recognition domains and bind sugars in different ways. Knowledge of how different domains bind sugars, combined with genomic information, makes it possible to provide an increasingly complete catalog of animal lectins. Examples of C-type lectins as well as other lectin families will be presented. Sugar-binding activity for endogenous mammalian glycans is better understood than binding of sugars on micro-organisms, such as bacteria, fungi, viruses and parasites, but recent progress in understanding such interactions will be discussed.
Title: Siglecs
Matthew Macauley
Siglecs are transmembrane receptors that recognize sialic acid-containing glycoconjugates. Expressed predominantly on immune cells, the majority of Siglecs have signaling motifs on their cytoplasmic tails that can repress immune cell signal. This is in line with the hypothesis that Siglecs recognize sialoglycans as a form of 'self’ recognition to limit autoimmunity. A combination of chemistry and genetics have accelerated our understanding of the precise biochemical nature of sialic acid ligands for Siglecs, with new findings demonstrating that Siglecs are specific for aspects of the glycan behind the linkage of the sialic acid to the underlying protein/lipid. For example, new studies point to the importance of the class of glycan, carbohydrate sulfation, and the specific protein(s) to which the glycan is appended. In parallel with advances in our understanding of their ligands, many new roles for Siglecs are being discovered in diseased states such as cancer, autoimmunity, and neurodegeneration.
Title: How structure leads to functions of the C-type lectins
Kurt Drickamer
Structural information is now available for most, although not all, of the carbohydrate-recognition domains of the C-type lectins in complex with glycan ligands. Combined with glycan array analysis and analysis of naturally occurring variants and introduced mutations, selective targeting of both host and pathogen glycans can often be explained. It is less well understood how these binding events mediate downstream effects of sugar binding, such as intracellular signaling, endocytosis, cell adhesion and complement fixation. However, the available structural information provides useful insights into possible mechanisms, both explaining the natural functions of the receptors and potentially facilitating manipulation of receptor functions using synthetic ligands.
