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-Structure paper
| タイトル | Myeloperoxidase transforms chromatin into neutrophil extracellular traps. |
|---|---|
| ジャーナル・号・ページ | Nature, Vol. 647, Issue 8090, Page 747-756, Year 2025 |
| 掲載日 | 2025年9月17日 |
著者 | Garth Lawrence Burn / Tobias Raisch / Sebastian Tacke / Moritz Winkler / Daniel Prumbaum / Stephanie Thee / Niclas Gimber / Stefan Raunser / Arturo Zychlinsky / ![]() |
| PubMed 要旨 | Neutrophils, the most abundant and biotoxic immune cells, extrude nuclear DNA into the extracellular space to maintain homeostasis. Termed neutrophil extracellular traps (NETs), these protein- ...Neutrophils, the most abundant and biotoxic immune cells, extrude nuclear DNA into the extracellular space to maintain homeostasis. Termed neutrophil extracellular traps (NETs), these protein-modified and decondensed extracellular DNA scaffolds control infection and are involved in coagulation, autoimmunity and cancer. Here we show how myeloperoxidase (MPO), a highly expressed neutrophil protein, disassembles nucleosomes, thereby facilitating NET formation, yet also binds stably to NETs extracellularly. We describe how the oligomeric status of MPO governs both outcomes. MPO dimers interact with nucleosomal DNA using one protomer and concurrently dock into the nucleosome acidic patch with the other protomer. As a consequence, dimeric MPO displaces DNA from the core complex, culminating in nucleosome disassembly. On the other hand, MPO monomers stably interact with the nucleosome acidic patch without making concomitant DNA contacts, explaining how monomeric MPO binds to and licences NETs to confer hypohalous acid production in the extracellular space. Our data demonstrate that the binding of MPO to chromatin is governed by specific molecular interactions that transform chromatin into a non-replicative, non-encoding state that offers new biological functions in a cell-free manner. We propose that MPO is, to our knowledge, the first member of a class of proteins that convert chromatin into an immune effector. |
リンク | Nature / PubMed:40963017 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.79 - 3.99 Å |
| 構造データ | EMDB-51295, PDB-9gen: EMDB-51296, PDB-9geo: EMDB-51297, PDB-9gep: ![]() EMDB-51298: Native dimeric Myeloperoxidase bound to nucleosome core particle; nucleosome focused map ![]() EMDB-51299: Native dimeric Myeloperoxidase bound to nucleosome core particle; MPO focused map ![]() EMDB-51300: Native dimeric Myeloperoxidase bound to nucleosome core particle; consensus map EMDB-51301, PDB-9geq: ![]() EMDB-51302: Native dimeric Myeloperoxidase bound to nucleosome core particle, intermediate state, nucleosome focused map ![]() EMDB-51303: Native dimeric Myeloperoxidase bound to nucleosome core particle, intermediate state, map focused on MPO ![]() EMDB-51304: Native dimeric Myeloperoxidase bound to nucleosome core particle, intermediate state, consensus map EMDB-51305, PDB-9ger: ![]() EMDB-51306: Native monomeric Myeloperoxidase bound to nucleosome core particle, late time point EMDB-52865, PDB-9ihd: EMDB-52866, PDB-9ihe: ![]() EMDB-52867: Nucleosome core particle bound by one monomer and one dimer of of DTT-reduced native myeloperoxidase; map focused on nucleosome/MPO monomer ![]() EMDB-52868: Nucleosome core particle bound by one monomer and one dimer of of DTT-reduced native myeloperoxidase; map focused on MPO dimer ![]() EMDB-52869: Nucleosome core particle bound by one monomer and one dimer of of DTT-reduced native myeloperoxidase; consensus map EMDB-52870, PDB-9ihf: |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-HOH: ![]() ChemComp-HEM: ![]() ChemComp-CL: ![]() ChemComp-CA: |
| 由来 |
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キーワード | IMMUNE SYSTEM / Peroxidase / innate immunity / histone / acidic patch / NUCLEAR PROTEIN / NETs |
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