A comprehensive N-glycoproteome atlas reveals tissue-specific glycan remodeling but non-random structural microheterogeneities.

Abstract

The mouse is a key model in biomedical research, yet its tissue-specific glycoproteome remains incompletely characterized due to glycan complexity and microheterogeneity. Here, we present a comprehensive N-glycoproteomic atlas across 24 mouse tissues, comprising 3045 N-glycans with distinct structural features attached at 8681 glycosites on 74,277 glycopeptides and 5026 glycoproteins. Among these glycans, 2687 (88.2%) meet the high-confidence threshold through an integrative confidence-estimation framework. Overall glycan structural patterns show enormous tissue-specific diversities, acting as superior molecular signatures of tissue identity and system origins. Notably, even commonly expressed glycoproteins undergo tissue-dependent glycan remodeling, suggesting that glycosylation may fine-tune protein functions to meet specialized biological demands. These patterns are further shaped by subcellular localization, which constrains glycan variabilities across compartments. Co-occurrence network analyses also expose substructural biases and non-random microheterogeneities among glycans attached at the same glycosites. The dataset serves as a valuable database resource for advancing the structural and functional understanding of glycoproteins.