Structural Insights into Biological Roles of Protein-Heparan Sulfate Interactions

Abstract

Glycosylation is the most common post-translational modifications which results in the addition of carbohydrate determinants, called glycans, to cell surface proteins and lipids. These glycan structures composes the "glycome", which plays an integral role in many biological processes. Glycosylation is increasingly recognized as a modulator of the malignant phenotype of cancer cells, where the interaction between cells and the tumor micro-environment is altered to facilitate processes such as drug resistance and metastasis. It has been notoriously difficult to study glycoproteins by mass spectrometry since the glycan moieties usually have an heterogeneous chemical structure and conformation. Besides, these glycan moieties are often mobile, as can be exemplified by heparan sulfate proteoglycan, which are heavily glycosylated and sulfated. However, analytical challenges in the tandem mass spectrometric analysis have been performed to minimize the neutral loss of information regarding to sulfated group structures. Unfortunately, there no structural work at detailed chemical level for proteoglycans. In addition, this knowledge is critical for our group because we identified partners of syndecan-1, and we need to further explore the interface of interaction as we performed previously (Aragão et al., 2012). Therefore, the aim of this study is to characterize the heparin sulfate structure of syndecan-1 using mass spectrometry technology to obtain information from glycomics and the interface of interaction among partners to understand the signaling between syndenca-1 and its partner. In addition, this expertise will allow the development of new projects in the area of glycomics. Understanding the roles of HSPG in cancer physiopathology is associated with the ability to determine the structures and abundances of HS.