Fine-Mapping of the Human Blood Plasma N-Glycome onto Its Proteome

Metabolites

Irena Trbojević-Akmačić¹  Gordan Lauc¹  Ivo Ugrina¹  Dennis O. Mook-Kanamori²  Karsten Suhre³  Tim Spector⁴  Mario Falchi⁴  Johannes Graumann⁵ 

[1] BICRO BIOCentar, Glycoscience Research Laboratory, Genos Ltd., Borongajska cesta 83H, 10000 Zagreb, Croatia;Department of Clinical Epidemiology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, The Netherlands;Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Education City, PO 24144, Doha, Qatar;Department of Twin Research and Genetic Epidemiology, King’s College London, London SE1 7EH, UK;Scientific Service Group Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, W.G. Kerckhoff Institute, Ludwigstr. 43, D-61231 Bad Nauheim, Germany;

关键词: glycomics;    proteomics;    N-glycosylation;    population study;    aptamers;    HILIC-UPLC;    SOMAscan;   

DOI  :  10.3390/metabo9070122

来源: DOAJ

【 摘 要 】

Most human proteins are glycosylated. Attachment of complex oligosaccharides to the polypeptide part of these proteins is an integral part of their structure and function and plays a central role in many complex disorders. One approach towards deciphering this human glycan code is to study natural variation in experimentally well characterized samples and cohorts. High-throughput capable large-scale methods that allow for the comprehensive determination of blood circulating proteins and their glycans have been recently developed, but so far, no study has investigated the link between both traits. Here we map for the first time the blood plasma proteome to its matching N-glycome by correlating the levels of 1116 blood circulating proteins with 113 N-glycan traits, determined in 344 samples from individuals of Arab, South-Asian, and Filipino descent, and then replicate our findings in 46 subjects of European ancestry. We report protein-specific N-glycosylation patterns, including a correlation of core fucosylated structures with immunoglobulin G (IgG) levels, and of trisialylated, trigalactosylated, and triantennary structures with heparin cofactor 2 (SERPIND2). Our study reveals a detailed picture of protein N-glycosylation and suggests new avenues for the investigation of its role and function in the associated complex disorders.

【 授权许可】

Unknown