title: N-glycoprotein macroheterogeneity: biological implications and proteomic characterization.
abstract: Glycosylation is a co- and post-translational modification that is critical for the regulation of the biophysical properties and biological activities of diverse proteins. Biosynthetic pathways for protein glycosylation are inherently inefficient, resulting in high structural diversity in mature glycoproteins. Macroheterogeneity is the structural diversity due to the presence or absence of glycans at specific glycosylation sites, and is caused by inefficiency in the initial transfer of glycans to proteins. Here, we review the enzymatic and evolutionary mechanisms controlling macroheterogeneity, its biological consequences in physiological and disease states, its relevance to heterologous production and glycoengineering of glycoproteins, and mass spectrometry based methods for its analysis. We highlight the importance of the analysis of macroheterogeneity for a complete understanding of glycoprotein biosynthesis and function, and emphasize how advances in mass spectrometry glycoproteomics will enable analysis of this critical facet of glycoprotein structural diversity.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, 4072, Australia.|Fundacion Instituto Leloir, Avenida Patricias Argentinas 435, Ciudad Autonoma de Buenos Aires, 1405, Argentina.
authors.forename: Lucia F
authors.initials: LF
authors.lastname: Zacchi
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Queensland, 4072, Australia. b.schulz@uq.edu.au.
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Schulz
mesh_terms: D000818:Animals; D006023:Glycoproteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000737:chemistry* / Q000145:classification / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D020543:Proteome
keywords: Glycoprotein; Glycoproteomics; Glycosylation; Macroheterogeneity; Mass spectrometry