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Poster De Conférence Année : 2021

Seeing is believing: glycosylation in the crystal structure of human myeloperoxidase

Résumé

Human myeloperoxidase (MPO) was first isolated in 1941 from purulent pleuritis fluid from tuberculosis patients. When neutrophilic polymorphonuclear leukocytes (neutrophils) entrap microbial or other invasive particulates, they release MPO during degranulation. In a respiratory burst of highly reactive oxygen species, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, from hydrogen peroxide. Mammalian MPO crystal structures were progressively acquired and entered in the Protein Data Bank (PDB) with partial glycosylation identification. Actually, the N-glycan composition of native MPO had been thoroughly investigated with mass spectrometry and shows 5 N-glycans at positions 323, 355, 391, 483 and 729 (1). Recently, MPO's enzymatic activity was reported to depend on the hyper-truncation of 2 out of 5 N-glycosylation sites (2). In our obtained crystal structure at 2.6 Å resolution containing 4 disulfide-linked homodimers of MPO, an interesting collection of glycans have been characterized. We compared those with the glycans from proteomics studies (1-3) and from 18 human MPO structures in the PDB. We made use of the Symbol Nomenclature for Glycans (SNFG) to illustrate congruence in the experimental data. We found each of the 5 glycosylation sites either non-glycosylated or glycosylated with paucimannosidic, high-mannose and complex N-glycans, with the hypertruncated N-acetyl-β-D-glucosamine core-type asparagine-linked glycans on Asn355 or Asn391 sites gate keeping the funnel towards the ROS-activated heme group. More experimental data on the glycosylation of MPO is hereby provided. Results b) Tjondro et al. (2) a) Reiding et al., (3)
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Dates et versions

hal-03323513 , version 1 (21-08-2021)

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  • HAL Id : hal-03323513 , version 1

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Lucas Krawczyk, Shubham Semwal, Goedele Roos, Pierre van Antwerpen, Julie Bouckaert. Seeing is believing: glycosylation in the crystal structure of human myeloperoxidase. A special symposium celebrating the 50th anniversary of the Protein Data Bank, May 2021, online, France. ⟨hal-03323513⟩

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