Structural insights into ubiquitin chain cleavage by Legionella ovarian tumor deubiquitinases
© 2023 Kang et al..
Although ubiquitin is found only in eukaryotes, several pathogenic bacteria and viruses possess proteins that hinder the host ubiquitin system. Legionella, a gram-negative intracellular bacterium, possesses an ovarian tumor (OTU) family of deubiquitinases (Lot DUBs). Herein, we describe the molecular characteristics of Lot DUBs. We elucidated the structure of the LotA OTU1 domain and revealed that entire Lot DUBs possess a characteristic extended helical lobe that is not found in other OTU-DUBs. The structural topology of an extended helical lobe is the same throughout the Lot family, and it provides an S1' ubiquitin-binding site. Moreover, the catalytic triads of Lot DUBs resemble those of the A20-type OTU-DUBs. Furthermore, we revealed a unique mechanism by which LotA OTU domains cooperate together to distinguish the length of the chain and preferentially cleave longer K48-linked polyubiquitin chains. The LotA OTU1 domain itself cleaves K6-linked ubiquitin chains, whereas it is also essential for assisting the cleavage of longer K48-linked polyubiquitin chains by the OTU2 domain. Thus, this study provides novel insights into the structure and mechanism of action of Lot DUBs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
Life science alliance - 6(2023), 7 vom: 26. Juli |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kang, Sangwoo [VerfasserIn] |
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| Links: |
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| Themen: |
120904-94-1 |
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| Anmerkungen: |
Date Completed 28.04.2023 Date Revised 18.08.2023 published: Electronic-Print PDB: 7W54, 8GOK, 4BOP, 3PHX, 7F9X, 6KS5, 7BU0, 6YK8, 2VFJ, 6W9R, 2ZFY Citation Status MEDLINE |
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| doi: |
10.26508/lsa.202201876 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356040658 |
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| 245 | 1 | 0 | |a Structural insights into ubiquitin chain cleavage by Legionella ovarian tumor deubiquitinases |
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| 500 | |a Date Completed 28.04.2023 | ||
| 500 | |a Date Revised 18.08.2023 | ||
| 500 | |a published: Electronic-Print | ||
| 500 | |a PDB: 7W54, 8GOK, 4BOP, 3PHX, 7F9X, 6KS5, 7BU0, 6YK8, 2VFJ, 6W9R, 2ZFY | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Kang et al. | ||
| 520 | |a Although ubiquitin is found only in eukaryotes, several pathogenic bacteria and viruses possess proteins that hinder the host ubiquitin system. Legionella, a gram-negative intracellular bacterium, possesses an ovarian tumor (OTU) family of deubiquitinases (Lot DUBs). Herein, we describe the molecular characteristics of Lot DUBs. We elucidated the structure of the LotA OTU1 domain and revealed that entire Lot DUBs possess a characteristic extended helical lobe that is not found in other OTU-DUBs. The structural topology of an extended helical lobe is the same throughout the Lot family, and it provides an S1' ubiquitin-binding site. Moreover, the catalytic triads of Lot DUBs resemble those of the A20-type OTU-DUBs. Furthermore, we revealed a unique mechanism by which LotA OTU domains cooperate together to distinguish the length of the chain and preferentially cleave longer K48-linked polyubiquitin chains. The LotA OTU1 domain itself cleaves K6-linked ubiquitin chains, whereas it is also essential for assisting the cleavage of longer K48-linked polyubiquitin chains by the OTU2 domain. Thus, this study provides novel insights into the structure and mechanism of action of Lot DUBs | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Kim, Gyuhee |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Minhyeong |e verfasserin |4 aut | |
| 700 | 1 | |a Jeong, Minwoo |e verfasserin |4 aut | |
| 700 | 1 | |a van der Heden van Noort, Gerbrand J |e verfasserin |4 aut | |
| 700 | 1 | |a Roh, Soung-Hun |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Donghyuk |e verfasserin |4 aut | |
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