An intrinsic network of polar interactions is responsible for binding of UL49.5 C-degron by the CRL2KLHDC3 ubiquitin ligase
© 2023 Wiley Periodicals LLC..
Bovine herpesvirus type 1 (BoHV-1) is a pathogen of cattle responsible for infectious bovine rhinotracheitis. The BoHV-1 UL49.5 is a transmembrane protein that binds to the transporter associated with antigen processing (TAP) and downregulates cell surface expression of the antigenic peptide complexes with the major histocompatibility complex class I (MHC-I). KLHDC3 is a kelch domain-containing protein 3 and a substrate receptor of a cullin2-RING (CRL2) E3 ubiquitin ligase. Recently, it has been identified that CRL2KLHDC3 is responsible for UL49.5-triggered TAP degradation via a C-degron pathway and the presence of the degron sequence does not lead to the degradation of UL49.5 itself. The molecular modeling of KLHDC3 in complexes with four UL49.5 C-terminal decapeptides (one native protein and three mutants) revealed their activity to be closely correlated with the conformation which they adopt in KLHDC3 binding cleft. To analyze the interaction between UL49.5 and KLHDC3 in detail, in this work a total of 3.6 μs long molecular dynamics simulations have been performed. The complete UL49.5-KLHDC3 complexes were embedded into the fully hydrated all-atom lipid membrane model with explicit water molecules. The network of polar interactions has been proposed to be responsible for the recognition and binding of the degron in KLHDC3. The interaction network within the binding pocket appeared to be very similar between two CRL2 substrate receptors: KLHDC3 and KLHDC2.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:92 |
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| Enthalten in: |
Proteins - 92(2024), 5 vom: 23. Apr., Seite 610-622 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ślusarz, Magdalena J [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 23.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/prot.26651 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365603740 |
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| 100 | 1 | |a Ślusarz, Magdalena J |e verfasserin |4 aut | |
| 245 | 1 | 3 | |a An intrinsic network of polar interactions is responsible for binding of UL49.5 C-degron by the CRL2KLHDC3 ubiquitin ligase |
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| 500 | |a Date Revised 23.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 Wiley Periodicals LLC. | ||
| 520 | |a Bovine herpesvirus type 1 (BoHV-1) is a pathogen of cattle responsible for infectious bovine rhinotracheitis. The BoHV-1 UL49.5 is a transmembrane protein that binds to the transporter associated with antigen processing (TAP) and downregulates cell surface expression of the antigenic peptide complexes with the major histocompatibility complex class I (MHC-I). KLHDC3 is a kelch domain-containing protein 3 and a substrate receptor of a cullin2-RING (CRL2) E3 ubiquitin ligase. Recently, it has been identified that CRL2KLHDC3 is responsible for UL49.5-triggered TAP degradation via a C-degron pathway and the presence of the degron sequence does not lead to the degradation of UL49.5 itself. The molecular modeling of KLHDC3 in complexes with four UL49.5 C-terminal decapeptides (one native protein and three mutants) revealed their activity to be closely correlated with the conformation which they adopt in KLHDC3 binding cleft. To analyze the interaction between UL49.5 and KLHDC3 in detail, in this work a total of 3.6 μs long molecular dynamics simulations have been performed. The complete UL49.5-KLHDC3 complexes were embedded into the fully hydrated all-atom lipid membrane model with explicit water molecules. The network of polar interactions has been proposed to be responsible for the recognition and binding of the degron in KLHDC3. The interaction network within the binding pocket appeared to be very similar between two CRL2 substrate receptors: KLHDC3 and KLHDC2 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a BoHV‐1 | |
| 650 | 4 | |a KLHDC3 | |
| 650 | 4 | |a PROTAC | |
| 650 | 4 | |a UL49.5 | |
| 650 | 4 | |a molecular dynamics | |
| 650 | 4 | |a protein degradation | |
| 650 | 4 | |a ubiquitin ligase | |
| 650 | 7 | |a Membrane Transport Proteins |2 NLM | |
| 650 | 7 | |a Ubiquitin |2 NLM | |
| 650 | 7 | |a Ubiquitin-Protein Ligases |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a Viral Envelope Proteins |2 NLM | |
| 650 | 7 | |a UL49.5 protein, bovine herpesvirus type 1 |2 NLM | |
| 700 | 1 | |a Lipińska, Andrea D |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Proteins |d 1988 |g 92(2024), 5 vom: 23. Apr., Seite 610-622 |w (DE-627)NLM012942030 |x 1097-0134 |7 nnns |
| 773 | 1 | 8 | |g volume:92 |g year:2024 |g number:5 |g day:23 |g month:04 |g pages:610-622 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1002/prot.26651 |3 Volltext |
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