Emerging Paradigms in Glycobiology.

Modern glycobiology is a result of multiple revolutionary and ground-breaking observations that both challenged and eventually changed prior perspectives about the expression and biological roles of glycoconjugates. These sweeping transformations in the field altered concepts that were embedded in what may be termed paradigms. Some prior paradigms included ideas that are still echoed in the current scientific literature, such as glycosylation of proteins is only found on secreted and membrane-associated proteins; glycans do not have clear and specific functions; protein binding to carbohydrates is relatively low affinity and non-specific; and protein glycosylation is relatively random and highly heterogeneous. As prior paradigms reached a crisis in terms of their supportability, they were replaced by new paradigms. The number of such new paradigms is large and documenting them is important. These modern paradigms include the idea that wide-spread modifications of amino acids with different sugars are common, that specific protein glycosylation occurs, the presence of glycoproteins in all cellular compartments, numerous roles of glycans and genes encoding their synthesis in human diseases, and the nature of carbohydrate recognition beyond simple sugars, and many others. Many researchers may not be aware of these emerging paradigms that have been developing in the research community since the 1960s. Here we summarize these new paradigms and some are discussed in detail from an historical perspective. These new paradigms demonstrate the essentiality and novelty of glycans and their biological functions.