Connecting single-nucleotide polymorphisms, glycosylation status, and interactions of plasma serine protease inhibitors

Understanding the combined impacts of genetic variances and post-translational modifications requires new approaches. Here, we delineate proteoforms plasma serine protease inhibitors relate specific to their interactions in complexes through use native mass spectrometry (MS). First, dissect proteoform repertoire an acute-phase protein, inhibitor A1 (SERPINA1), resolving four SERPINA1 variants (M1V, M1A, M2, M3) with common single-nucleotide polymorphisms (SNPs). Investigating glycosylation status these ability form a protease, elastase, find that fucosylation stabilizes interaction M1V variant its core on Asn271. In contrast, antennary Asn271 destabilizes SERPINA1-elastase interactions. We unveil same opposing effects SERPINA3 chymotrypsin. Together, our MS results highlight modulating different linkages glycoprotein