FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3045131911> ?p ?o ?g. }

• W3045131911 abstract "Abstract Myeloperoxidase (MPO) plays essential roles in neutrophil-mediated immunity via the generation of reactive oxidation products. Complex carbohydrates decorate MPO at discrete sites, but their functional relevance remain elusive. To this end, we have characterised the structure-biosynthesis-activity relationship of neutrophil MPO (nMPO). Mass spectrometry demonstrated that nMPO carries both characteristic under-processed and hyper-truncated glycans. Occlusion of the Asn355/Asn391-glycosylation sites and the Asn323-/Asn483-glycans, located in the MPO dimerisation zone, was found to affect the local glycan processing, thereby providing a molecular basis of the site-specific nMPO glycosylation. Native mass spectrometry, mass photometry, and glycopeptide profiling revealed significant molecular complexity of diprotomeric nMPO arising from heterogeneous glycosylation, oxidation, chlorination and polypeptide truncation variants, and a previously unreported low-abundance monomer. Longitudinal profiling of maturing, mature, granule-separated, and pathogen-stimulated neutrophils demonstrated that nMPO is dynamically expressed during granulopoiesis, unevenly distributed across granules and degranulated upon activation. We also show that proMPO-to-MPO maturation occurs during early/mid-stage granulopoiesis. While similar global MPO glycosylation was observed across conditions, the conserved Asn355-/Asn391-sites displayed elevated glycan hyper-truncation, which correlated with higher enzyme activities of MPO in distinct granule populations. Enzymatic trimming of the Asn355-/Asn391-glycans recapitulated the activity gain and showed that nMPO carrying hyper-truncated glycans at these positions exhibits increased thermal stability, polypeptide accessibility, and ceruloplasmin-mediated inhibition potential relative to native nMPO. Finally, structural modelling revealed that hyper-truncated Asn355-glycans positioned in the MPO-ceruloplasmin interface are critical for uninterrupted inhibition. Here, through an innovative and comprehensive approach, we report novel functional roles of MPO glycans, providing new insight into neutrophil-mediated immunity. Significance Myeloperoxidase (MPO) is an important microbicidal glycoprotein critical for fighting pathogens. We report, for the first time, the intriguingly complex relationship between glycobiology and MPO immune function by demonstrating that uncommon and strategically positioned hyper-truncated glycans both elevate the activity and the inhibition potential of this pathogen-combating enzyme. We have used a multifaceted approach employing integrated biomolecular analytics to generate new insights into the sugar code of MPO. The findings described in this study improve our understanding of key innate immune processes and may guide future glycoengineering efforts aiming to generate therapeutically relevant recombinant MPO products with tuneable activity and inhibition potential tailored to biomedical applications involving persisting and severe pathogen infections." @default.
• W3045131911 created "2020-07-29" @default.
• W3045131911 creator A5011647620 @default.
• W3045131911 creator A5012415731 @default.
• W3045131911 creator A5017253735 @default.
• W3045131911 creator A5021967170 @default.
• W3045131911 creator A5024730956 @default.
• W3045131911 creator A5026046629 @default.
• W3045131911 creator A5037819491 @default.
• W3045131911 creator A5040145749 @default.
• W3045131911 creator A5040291432 @default.
• W3045131911 creator A5046627688 @default.
• W3045131911 creator A5059222256 @default.
• W3045131911 creator A5062545403 @default.
• W3045131911 creator A5067151082 @default.
• W3045131911 creator A5081186229 @default.
• W3045131911 creator A5083205806 @default.
• W3045131911 creator A5086719622 @default.
• W3045131911 creator A5086855668 @default.
• W3045131911 creator A5090521668 @default.
• W3045131911 date "2020-07-25" @default.
• W3045131911 modified "2023-09-26" @default.
• W3045131911 title "Hyper-Truncated Glycans Augment the Activity of Neutrophil Granule Myeloperoxidase" @default.
• W3045131911 cites W1532795681 @default.
• W3045131911 cites W1886998470 @default.
• W3045131911 cites W1971435128 @default.
• W3045131911 cites W1974328198 @default.
• W3045131911 cites W1989947263 @default.
• W3045131911 cites W1993838215 @default.
• W3045131911 cites W2001328992 @default.
• W3045131911 cites W2024738256 @default.
• W3045131911 cites W2041309279 @default.
• W3045131911 cites W2041647620 @default.
• W3045131911 cites W2059149560 @default.
• W3045131911 cites W2063747968 @default.
• W3045131911 cites W2067354761 @default.
• W3045131911 cites W2080077198 @default.
• W3045131911 cites W2080752012 @default.
• W3045131911 cites W2083529126 @default.
• W3045131911 cites W2084766054 @default.
• W3045131911 cites W2088424323 @default.
• W3045131911 cites W2096578491 @default.
• W3045131911 cites W2105633984 @default.
• W3045131911 cites W2109173122 @default.
• W3045131911 cites W2135423890 @default.
• W3045131911 cites W2139700389 @default.
• W3045131911 cites W2142122443 @default.
• W3045131911 cites W2147070585 @default.
• W3045131911 cites W2147215195 @default.
• W3045131911 cites W2149568646 @default.
• W3045131911 cites W2150737376 @default.
• W3045131911 cites W2155490209 @default.
• W3045131911 cites W2160748613 @default.
• W3045131911 cites W2161894245 @default.
• W3045131911 cites W2172680325 @default.
• W3045131911 cites W2190199302 @default.
• W3045131911 cites W2207172782 @default.
• W3045131911 cites W2276080164 @default.
• W3045131911 cites W2291786253 @default.
• W3045131911 cites W2304125728 @default.
• W3045131911 cites W2334348545 @default.
• W3045131911 cites W2414983659 @default.
• W3045131911 cites W2517949416 @default.
• W3045131911 cites W2522141296 @default.
• W3045131911 cites W2587049291 @default.
• W3045131911 cites W2601129450 @default.
• W3045131911 cites W2674157678 @default.
• W3045131911 cites W2788405691 @default.
• W3045131911 cites W2791572784 @default.
• W3045131911 cites W2794525690 @default.
• W3045131911 cites W2794631000 @default.
• W3045131911 cites W2795010423 @default.
• W3045131911 cites W2795278503 @default.
• W3045131911 cites W2801919855 @default.
• W3045131911 cites W2892064913 @default.
• W3045131911 cites W2917685341 @default.
• W3045131911 cites W2923914572 @default.
• W3045131911 cites W2943316932 @default.
• W3045131911 cites W2968144457 @default.
• W3045131911 cites W2986829891 @default.
• W3045131911 cites W2991375047 @default.
• W3045131911 cites W3043669394 @default.
• W3045131911 cites W3046370131 @default.
• W3045131911 cites W3081266271 @default.
• W3045131911 cites W4236235247 @default.
• W3045131911 cites W4242282932 @default.
• W3045131911 cites W4244209136 @default.
• W3045131911 cites W9802559 @default.
• W3045131911 cites W4235079871 @default.
• W3045131911 hasPublicationYear "2020" @default.
• W3045131911 type Work @default.
• W3045131911 sameAs 3045131911 @default.
• W3045131911 citedByCount "0" @default.
• W3045131911 crossrefType "posted-content" @default.
• W3045131911 hasAuthorship W3045131911A5011647620 @default.
• W3045131911 hasAuthorship W3045131911A5012415731 @default.
• W3045131911 hasAuthorship W3045131911A5017253735 @default.
• W3045131911 hasAuthorship W3045131911A5021967170 @default.
• W3045131911 hasAuthorship W3045131911A5024730956 @default.
• W3045131911 hasAuthorship W3045131911A5026046629 @default.

• next