title: Human plasma protein N-glycosylation.
abstract: Glycosylation is the most abundant and complex protein modification, and can have a profound structural and functional effect on the conjugate. The oligosaccharide fraction is recognized to be involved in multiple biological processes, and to affect proteins physical properties, and has consequentially been labeled a critical quality attribute of biopharmaceuticals. Additionally, due to recent advances in analytical methods and analysis software, glycosylation is targeted in the search for disease biomarkers for early diagnosis and patient stratification. Biofluids such as saliva, serum or plasma are of great use in this regard, as they are easily accessible and can provide relevant glycosylation information. Thus, as the assessment of protein glycosylation is becoming a major element in clinical and biopharmaceutical research, this review aims to convey the current state of knowledge on the N-glycosylation of the major plasma glycoproteins alpha-1-acid glycoprotein, alpha-1-antitrypsin, alpha-1B-glycoprotein, alpha-2-HS-glycoprotein, alpha-2-macroglobulin, antithrombin-III, apolipoprotein B-100, apolipoprotein D, apolipoprotein F, beta-2-glycoprotein 1, ceruloplasmin, fibrinogen, immunoglobulin (Ig) A, IgG, IgM, haptoglobin, hemopexin, histidine-rich glycoprotein, kininogen-1, serotransferrin, vitronectin, and zinc-alpha-2-glycoprotein. In addition, the less abundant immunoglobulins D and E are included because of their major relevance in immunology and biopharmaceutical research. Where available, the glycosylation is described in a site-specific manner. In the discussion, we put the glycosylation of individual proteins into perspective and speculate how the individual proteins may contribute to a total plasma N-glycosylation profile determined at the released glycan level.
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Florent
authors.initials: F
authors.lastname: Clerc
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Karli R
authors.initials: KR
authors.lastname: Reiding
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Bas C
authors.initials: BC
authors.lastname: Jansen
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Guinevere S M
authors.initials: GS
authors.lastname: Kammeijer
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.|Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Bondt
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. m.wuhrer@lumc.nl.|Division of BioAnalytical Chemistry, VU University Amsterdam, Amsterdam, The Netherlands. m.wuhrer@lumc.nl.
authors.forename: Manfred
authors.initials: M
authors.lastname: Wuhrer
mesh_terms: D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D011499:Protein Processing, Post-Translational
chemical_list: D001798:Blood Proteins; D006023:Glycoproteins
keywords: Glycoproteins; Glycoproteomics; Immunoglobulins; N-glycosylation; Plasma; Serum