Functional implications of glycans and their curation: insights from the workshop held at the 16th Annual International Biocuration Conference in Padua, Italy.

Dynamic changes in protein glycosylation impact human health and disease progression. However, current resources that capture disease and phenotype information focus primarily on the macromolecules within the central dogma of molecular biology (DNA, RNA, proteins). To gain a better understanding of organisms, there is a need to capture the functional impact of glycans and glycosylation on biological processes.

A biological guide to glycosaminoglycans: current perspectives and pending questions.

Mammalian glycosaminoglycans (GAGs), except hyaluronan (HA), are sulfated polysaccharides that are covalently attached to core proteins to form proteoglycans (PGs). This article summarizes key biological findings for the most widespread GAGs, namely HA, chondroitin sulfate/dermatan sulfate (CS/DS), keratan sulfate (KS), and heparan sulfate (HS). It focuses on the major processes that remain to be deciphered to get a comprehensive view of the mechanisms mediating GAG biological functions.

LeishMANIAdb: a comparative resource for Leishmania proteins.

Leishmaniasis is a detrimental disease causing serious changes in quality of life and some forms can lead to death. The disease is spread by the parasite Leishmania transmitted by sandfly vectors and their primary hosts are vertebrates including humans. The pathogen penetrates host cells and secretes proteins (the secretome) to repurpose cells for pathogen growth and to alter cell signaling via host-pathogen protein-protein interactions).

Conformations, interactions and functions of intrinsically disordered syndecans.

Syndecans are transmembrane heparan sulfate proteoglycans present on most mammalian cell surfaces. They have a long evolutionary history, a single syndecan gene being expressed in bilaterian invertebrates. Syndecans have attracted interest because of their potential roles in development and disease, including vascular diseases, inflammation and various cancers.

Glycosaminoglycans: What Remains To Be Deciphered?

Glycosaminoglycans (GAGs) are complex polysaccharides exhibiting a vast structural diversity and fulfilling various functions mediated by thousands of interactions in the extracellular matrix, at the cell surface, and within the cells where they have been detected in the nucleus. It is known that the chemical groups attached to GAGs and GAG conformations comprise "glycocodes" that are not yet fully deciphered. The molecular context also matters for GAG structures and functions, and the influence of the structure and functions of the proteoglycan core proteins on sulfated GAGs and vice versa warrants further investigation.

Conditional expression of endorepellin in the tumor vasculature attenuates breast cancer growth, angiogenesis and hyaluronan deposition.

The tumor stroma of most solid malignancies is characterized by a pathological accumulation of pro-angiogenic and pro-tumorigenic hyaluronan driving tumorigenesis and metastatic potential. Of all three hyaluronan synthase isoforms, HAS2 is the primary enzyme that promotes the build-up of tumorigenic HA in breast cancer. Previously, we discovered that endorepellin, the angiostatic C-terminal fragment of perlecan, evokes a catabolic mechanism targeting endothelial HAS2 and hyaluronan via autophagic induction.

Building, Visualizing, and Analyzing Glycosaminoglycan-Protein Interaction Networks.

This chapter describes how to generate, visualize, and analyze interaction networks of glycosaminoglycans (GAGs), which are linear polyanionic polysaccharides mostly located at the cell surface and in the extracellular matrix. The protocol is divided into three major steps: (1) the collection of GAG-mediated interaction data, (2) the visualization of GAG interaction networks, and (3) the computational enrichment analyses of these networks to identify their overrepresented features (e.g.

Proteomics Standards Initiative at Twenty Years: Current Activities and Future Work.

The Human Proteome Organization (HUPO) Proteomics Standards Initiative (PSI) has been successfully developing guidelines, data formats, and controlled vocabularies (CVs) for the proteomics community and other fields supported by mass spectrometry since its inception 20 years ago. Here we describe the general operation of the PSI, including its leadership, working groups, yearly workshops, and the document process by which proposals are thoroughly and publicly reviewed in order to be ratified as PSI standards. We briefly describe the current state of the many existing PSI standards, some of which remain the same as when originally developed, some of which have undergone subsequent revisions, and some of which have become obsolete.

Impact of calcium ions on the structural and dynamic properties of heparin oligosaccharides by computational analysis.

Heparin (HP) belongs to glycosaminoglycans (GAGs), anionic linear polysaccharides composed of repetitive disaccharide units. They are key players in many biological processes occurring in the extracellular matrix and at the cell surface. GAGs are challenging molecules for computational research due to their high chemical heterogeneity, flexibility, periodicity, pseudosymmetry, predominantly electrostatics-driven nature of interactions with their protein partners and potential multipose binding.

The glycosaminoglycan interactome 2.0.

Glycosaminoglycans (GAGs) are complex linear polysaccharides, which are covalently attached to core proteins (except for hyaluronan) to form proteoglycans. They play key roles in the organization of the extracellular matrix, and at the cell surface where they contribute to the regulation of cell signaling and of cell adhesion. To explore the mechanisms and pathways underlying their functions, we have generated an expanded dataset of 4,290 interactions corresponding to 3,464 unique GAG-binding proteins, four times more than the first version of the GAG interactome (Vallet, Clerc, and Ricard-Blum.

Glycosaminoglycan interaction networks and databases.

Glycosaminoglycans are complex polysaccharides exhibiting a large structural and conformational diversity. These key biological players organize the extracellular matrix, contribute to cell-matrix interactions, and regulate cell signaling. Natural and synthetic libraries of glycosaminoglycans have been spotted on microarrays to find glycosaminoglycan partners and determine the size and the chemical groups promoting protein binding.

Multiscale modelling of the extracellular matrix.

The extracellular matrix is a complex three-dimensional network of molecules that provides cells with a complex microenvironment. The major constituents of the extracellular matrix such as collagen, elastin and associated proteins form supramolecular assemblies contributing to its physicochemical properties and organization. The structure of proteins and their supramolecular assemblies such as fibrils have been studied at the atomic level (e.

The IntAct database: efficient access to fine-grained molecular interaction data.

The IntAct molecular interaction database (https://www.ebi.ac.

Extended disorder at the cell surface: The conformational landscape of the ectodomains of syndecans.

Syndecans are membrane proteoglycans regulating extracellular matrix assembly, cell adhesion and signaling. Their ectodomains can be shed from the cell surface, and act as paracrine and autocrine effectors or as competitors of full-length syndecans. We report the first biophysical characterization of the recombinant ectodomains of the four human syndecans using biophysical techniques, and show that they behave like flexible random-coil intrinsically disordered proteins, and adopt several conformation ensembles in solution.

Building Protein-Protein and Protein-Glycosaminoglycan Interaction Networks Using MatrixDB, the Extracellular Matrix Interaction Database.

The interaction database MatrixDB reports protein-protein and protein-glycosaminoglycan interactions in human, mammalian, and model organisms, involving at least one extracellular matrix (ECM) constituent, namely full-length proteins, ECM multimeric proteins considered as stable complexes, proteoglycans, glycosaminoglycans (GAGs), and bioactive fragments called matricryptins, which are released upon limited proteolysis of ECM proteins. The current version of MatrixDB (as of October 2020) contains 106,543 experimentally supported interactions, with all types of biomolecules combined. MatrixDB is the only database focusing on the curation of ECM protein and GAG interactions.

Computational and experimental characterization of the novel ECM glycoprotein SNED1 and prediction of its interactome.

The extracellular matrix (ECM) is a complex meshwork of proteins and an essential component of multicellular life. We have recently reported the characterization of a novel ECM protein, SNED1, and showed that it promotes breast cancer metastasis and regulates craniofacial development. However, the mechanisms by which it does so remain unknown.

A guide to the composition and functions of the extracellular matrix.

Extracellular matrix (ECM) is a dynamic 3-dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over the last decade that ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties and morphology. Extracellularly secreted as well as cell-bound factors are among the major members of the ECM family.

The Interactome of Cancer-Related Lysyl Oxidase and Lysyl Oxidase-Like Proteins.

The members of the lysyl oxidase (LOX) family are amine oxidases, which initiate the covalent cross-linking of the extracellular matrix (ECM), regulate ECM stiffness, and contribute to cancer progression. The aim of this study was to build the first draft of the interactome of the five members of the LOX family in order to determine its molecular functions, the biological and signaling pathways mediating these functions, the biological processes it is involved in, and if and how it is rewired in cancer. In vitro binding assays, based on surface plasmon resonance and bio-layer interferometry, combined with queries of interaction databases and interaction datasets, were used to retrieve interaction data.

GAG-DB, the New Interface of the Three-Dimensional Landscape of Glycosaminoglycans.

Glycosaminoglycans (GAGs) are complex linear polysaccharides. GAG-DB is a curated database that classifies the three-dimensional features of the six mammalian GAGs (chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate) and their oligosaccharides complexed with proteins. The entries are structures of GAG and GAG-protein complexes determined by X-ray single-crystal diffraction methods, X-ray fiber diffractometry, solution NMR spectroscopy, and scattering data often associated with molecular modeling.

PED in 2021: a major update of the protein ensemble database for intrinsically disordered proteins.

The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.

The IMEx coronavirus interactome: an evolving map of Coronaviridae-host molecular interactions.

The current coronavirus disease of 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions can provide fine-grained resolution of the mechanisms behind the virus biology and the human organism response. We present a curated dataset of physical molecular interactions focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family that has been manually extracted by International Molecular Exchange (IMEx) Consortium curators.