DNA-mediated proteolysis by neutrophil elastase enhances binding activities of the HMGB1 protein
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
Neutrophil extracellular traps (NETs) are produced through ejection of genomic DNA by neutrophils into extracellular space and serve as a weapon to fight against pathogens. Neutrophil elastase, a serine protease loaded on NETs, attacks and kills pathogens, while extracellular high-mobility-group-box-1 (HMGB1) protein serves as a danger signal to other cells. How the action of these factors is coordinated as part of the innate immune response is not fully understood. In this article, using biochemical and biophysical approaches, we demonstrate that DNA mediates specific proteolysis of HMGB1 by neutrophil elastase and that the proteolytic processing remarkably enhances binding activities of extracellular HMGB1. Through the DNA-mediated proteolysis of HMGB1 by neutrophil elastase, the negatively charged segment containing D/E repeats is removed from HMGB1. This proteolytic removal of the C-terminal tail causes a substantial increase in binding activities of HMGB1 because the D/E repeats are crucial for dynamic autoinhibition via electrostatic interactions. Our data on the oxidized HMGB1 (i.e., 'disulfide HMGB1') protein show that the truncation substantially increases HMGB1's affinities for the toll-like receptor TLR4•MD-2 complex, DNA G-quadruplex, and the Holliday junction DNA structure. The DNA-mediated proteolysis of HMGB1 by neutrophil elastase in NETs may promote the function of extracellular HMGB1 as a damage-associated molecular pattern that triggers the innate immune response of nearby cells.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:298 |
|---|---|
| Enthalten in: |
The Journal of biological chemistry - 298(2022), 11 vom: 30. Nov., Seite 102577 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Xi [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 29.11.2022 Date Revised 08.12.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.jbc.2022.102577 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM347355706 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM347355706 | ||
| 003 | DE-627 | ||
| 005 | 20231226033628.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.jbc.2022.102577 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1157.xml |
| 035 | |a (DE-627)NLM347355706 | ||
| 035 | |a (NLM)36220391 | ||
| 035 | |a (PII)S0021-9258(22)01021-3 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Xi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a DNA-mediated proteolysis by neutrophil elastase enhances binding activities of the HMGB1 protein |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.11.2022 | ||
| 500 | |a Date Revised 08.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Neutrophil extracellular traps (NETs) are produced through ejection of genomic DNA by neutrophils into extracellular space and serve as a weapon to fight against pathogens. Neutrophil elastase, a serine protease loaded on NETs, attacks and kills pathogens, while extracellular high-mobility-group-box-1 (HMGB1) protein serves as a danger signal to other cells. How the action of these factors is coordinated as part of the innate immune response is not fully understood. In this article, using biochemical and biophysical approaches, we demonstrate that DNA mediates specific proteolysis of HMGB1 by neutrophil elastase and that the proteolytic processing remarkably enhances binding activities of extracellular HMGB1. Through the DNA-mediated proteolysis of HMGB1 by neutrophil elastase, the negatively charged segment containing D/E repeats is removed from HMGB1. This proteolytic removal of the C-terminal tail causes a substantial increase in binding activities of HMGB1 because the D/E repeats are crucial for dynamic autoinhibition via electrostatic interactions. Our data on the oxidized HMGB1 (i.e., 'disulfide HMGB1') protein show that the truncation substantially increases HMGB1's affinities for the toll-like receptor TLR4•MD-2 complex, DNA G-quadruplex, and the Holliday junction DNA structure. The DNA-mediated proteolysis of HMGB1 by neutrophil elastase in NETs may promote the function of extracellular HMGB1 as a damage-associated molecular pattern that triggers the innate immune response of nearby cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a DNA–protein interaction | |
| 650 | 4 | |a NMR | |
| 650 | 4 | |a fluorescence anisotropy | |
| 650 | 4 | |a protease | |
| 650 | 4 | |a protein processing | |
| 650 | 4 | |a toll-like receptor 4 | |
| 650 | 7 | |a Leukocyte Elastase |2 NLM | |
| 650 | 7 | |a EC 3.4.21.37 |2 NLM | |
| 650 | 7 | |a HMGB1 Protein |2 NLM | |
| 650 | 7 | |a DNA |2 NLM | |
| 650 | 7 | |a 9007-49-2 |2 NLM | |
| 700 | 1 | |a Mayorga-Flores, Marlen |e verfasserin |4 aut | |
| 700 | 1 | |a Bien, Karina G |e verfasserin |4 aut | |
| 700 | 1 | |a Bailey, Aaron O |e verfasserin |4 aut | |
| 700 | 1 | |a Iwahara, Junji |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The Journal of biological chemistry |d 1945 |g 298(2022), 11 vom: 30. Nov., Seite 102577 |w (DE-627)NLM000004995 |x 1083-351X |7 nnns |
| 773 | 1 | 8 | |g volume:298 |g year:2022 |g number:11 |g day:30 |g month:11 |g pages:102577 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.jbc.2022.102577 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 298 |j 2022 |e 11 |b 30 |c 11 |h 102577 | ||