Conformation of Glycopeptides and Glycoproteins

Abstract

Glycosylation is the most frequent post-translational modification found in proteins. Glycoproteins are involved in a highly diverse spectrum of biological functions, ranging from protein folding and molecular and cellular recognition to attack of pathogens and regulation of biological half-life. Consequently, understanding the structural role of glycosylation provides key insight into biological processes as well as ideas for medicinal applications. Here, we review the current methodology to arrive at highresolution structures of glycopeptides and glycoproteins. To achieve this, significant obstacles have to be overcome like preparation of sufficient amounts of sufficiently pure and homogeneous material, analyzing highly ambiguous spectroscopic data, and dealing with molecules that show local or global disorder. We will provide an overview of our knowledge of glycoprotein and glycopeptide structure, and illustrate with selected examples the performance and limitations of current methodology.

Secretion, isotopic labeling and deglycosylation of N-acylethanolamine acid amidase for biophysical studies

“…Chemical shift changes and measurable conformational changes have been observed in the vicinity of the glycosylation site [32,34] however global decreases in dynamic fluctuations have been measured with the attachment of as little as a single carbohydrate [32]. This is consistent with increased dynamics and a greater degree of signal averaging in the absence of glycosylation [32,33,35]. Thus for large proteins, flexible loops may be more dynamically rigid giving rise to complex spectra [33].…”

NMR Spectroscopic Studies of the Conformational Ensembles of Intrinsically Disordered Proteins

“…Thus, PTMs will contribute to this versatility by modulating and regulating their cellular location, activity and interaction properties (Deribe et al 2010). Additionally, due to the inherent flexibility of IDPs, PTMs will have large impacts on their conformational ensemble and alter their structural dynamics (Errington and Doig 2005;Maltsev et al 2012;Mao et al 2010;Meyer and Möller 2007;Theillet et al 2014). Unfortunately, so far, an overwhelming majority of NMR studies completely neglect the impact of PTMs on the properties and structural dynamics of IDPs and are consequently devoid of biological significance.…”

“…Both modifications are expected to have significant effects on the structural dynamics and interaction properties of IDPs (Meyer and Möller 2007). Tyrosine sulfation in particular has been shown to regulate many extracellular interactions (Kehoe and Bertozzi 2000).…”

The Role of Glycosylation in Receptor Signaling

“…The description of the role of viral glycoproteins in host-virus interactions have been studied extensively and reviewed in detail elsewhere (5). However, this important interaction deserves mention.…”