Glycosylation - February 2012

Figure 1 from Aich (2011) FEBS J 278: 1699-1712; Figure 6 from S. Pouilly et al (2012) FEBS J 279: 586-598; Figure 3 from E J A Veldhuizen et al (2011) FEBS J 278: 3930-3941

Published: 1 February 2012

Papers selected by: Dan Michele                              

To some, carbohydrate modifications of proteins are an annoying nuisance that prevents functional recombinant protein expression or complicates normal protein purification and characterization. To others, the complex, branched stereospecific linkages of glycans are beautiful puzzles to decode and study their function. The field of glycobiology continues to expand at an ever increasing rate. My college biochemistry textbook written in 1990, although touting the great accomplishments of the field in the prior 20 years, could only give a few classic examples of glycoprotein modifications with known function such as the role of proteoglycans in cartilage, the protective role of mucins in epithelium, and antifreeze glycoproteins of arctic fishes. That 1990 textbook in fact indicated that the function of the carbohydrates moieties on most glycoproteins remained “enigmatic”.

While many questions still remain, carbohydrate modifications of proteins have begun to lose their “enigmatic” classification. With the decoding of the human genome and a number of genomes from other species in the last decade and the ever-expanding toolbox to study the chemistry of glycan moieties, the rich diversity of protein glycosylation, the function of the enzymes mediating these beautiful functional decorations on proteins, and the critical role glycosylation in normal biology and human disease is becoming increasingly evident. The identification of important human genetic diseases caused by abnormal glycosylation, such as the multi-syndrome Congenital Disorders of Glycosylation, several forms of muscular dystrophy, glycosaminoglycan diseases such as Ehlers-Danlos Syndrome and chondrodysplasias, and many others, have pointed to the critical role of glycosylation in human health and disease. Furthermore, while many membrane proteins utilize glycans to interact with their extracellular environment, many pathogenic organisms, such as influenza, hemorrhagic fever viruses, and bacteria causing leprosy, hijack these same interactions to gain entry into cells. The growing diverse list of the roles of glycans in important human diseases makes the study of their synthesis, structure, and impact on protein and cellular function critical to our understanding of pathogenic mechanisms.

Our journal’s submissions in the field of glycobiology have reflected this rich diversity, with papers ranging from the study of the roles of glycoproteins in human disease and cellular biology, to explaining how glycans affect the production of the smell of ripe tomatoes (Louveau et al FEBSJ 2011), and the function of hormones in stick bugs (Munte et al FEBSJ 2008). To fully capture this diversity of manuscripts in a single Virtual Issue is impossible. Therefore, this Issue highlights recent papers in the journal demonstrating:

1) how state-of-the-art high-throughput and high-sensitivity glycomic approaches are deciphering new glycomic profiles to shed light on biological mechanisms and pathomechanisms of disease.

2) the mechanisms of how important cellular and protein functions are directly mediated by post-translational protein glycosylation

3) the translation of these newly found mechanisms toward novel “glyco- therapies” for treating important human diseases

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