HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160
© 2021 Liu et al..
HVEM is a TNF (tumor necrosis factor) receptor contributing to a broad range of immune functions involving diverse cell types. It interacts with a TNF ligand, LIGHT, and immunoglobulin (Ig) superfamily members BTLA and CD160. Assessing the functional impact of HVEM binding to specific ligands in different settings has been complicated by the multiple interactions of HVEM and HVEM binding partners. To dissect the molecular basis for multiple functions, we determined crystal structures that reveal the distinct HVEM surfaces that engage LIGHT or BTLA/CD160, including the human HVEM-LIGHT-CD160 ternary complex, with HVEM interacting simultaneously with both binding partners. Based on these structures, we generated mouse HVEM mutants that selectively recognized either the TNF or Ig ligands in vitro. Knockin mice expressing these muteins maintain expression of all the proteins in the HVEM network, yet they demonstrate selective functions for LIGHT in the clearance of bacteria in the intestine and for the Ig ligands in the amelioration of liver inflammation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:218 |
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| Enthalten in: |
The Journal of experimental medicine - 218(2021), 12 vom: 06. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Weifeng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.12.2021 Date Revised 26.02.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1084/jem.20211112 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM332476863 |
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| 100 | 1 | |a Liu, Weifeng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a HVEM structures and mutants reveal distinct functions of binding to LIGHT and BTLA/CD160 |
| 264 | 1 | |c 2021 | |
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| 500 | |a Date Completed 27.12.2021 | ||
| 500 | |a Date Revised 26.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 Liu et al. | ||
| 520 | |a HVEM is a TNF (tumor necrosis factor) receptor contributing to a broad range of immune functions involving diverse cell types. It interacts with a TNF ligand, LIGHT, and immunoglobulin (Ig) superfamily members BTLA and CD160. Assessing the functional impact of HVEM binding to specific ligands in different settings has been complicated by the multiple interactions of HVEM and HVEM binding partners. To dissect the molecular basis for multiple functions, we determined crystal structures that reveal the distinct HVEM surfaces that engage LIGHT or BTLA/CD160, including the human HVEM-LIGHT-CD160 ternary complex, with HVEM interacting simultaneously with both binding partners. Based on these structures, we generated mouse HVEM mutants that selectively recognized either the TNF or Ig ligands in vitro. Knockin mice expressing these muteins maintain expression of all the proteins in the HVEM network, yet they demonstrate selective functions for LIGHT in the clearance of bacteria in the intestine and for the Ig ligands in the amelioration of liver inflammation | ||
| 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 Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a Antigens, CD |2 NLM | |
| 650 | 7 | |a CD160 protein, human |2 NLM | |
| 650 | 7 | |a GPI-Linked Proteins |2 NLM | |
| 650 | 7 | |a Multiprotein Complexes |2 NLM | |
| 650 | 7 | |a Receptors, Immunologic |2 NLM | |
| 650 | 7 | |a Receptors, Tumor Necrosis Factor, Member 14 |2 NLM | |
| 650 | 7 | |a TNFRSF14 protein, human |2 NLM | |
| 650 | 7 | |a TNFSF14 protein, human |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor Ligand Superfamily Member 14 |2 NLM | |
| 700 | 1 | |a Chou, Ting-Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Garrett-Thomson, Sarah C |e verfasserin |4 aut | |
| 700 | 1 | |a Seo, Goo-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Fedorov, Elena |e verfasserin |4 aut | |
| 700 | 1 | |a Ramagopal, Udupi A |e verfasserin |4 aut | |
| 700 | 1 | |a Bonanno, Jeffrey B |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Qingyang |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kenneth |e verfasserin |4 aut | |
| 700 | 1 | |a Garforth, Scott J |e verfasserin |4 aut | |
| 700 | 1 | |a Kakugawa, Kiyokazu |e verfasserin |4 aut | |
| 700 | 1 | |a Cheroutre, Hilde |e verfasserin |4 aut | |
| 700 | 1 | |a Kronenberg, Mitchell |e verfasserin |4 aut | |
| 700 | 1 | |a Almo, Steven C |e verfasserin |4 aut | |
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