Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family
Tripartite motif (TRIM) proteins constitute one of the largest subfamilies of the RING-type E3 ubiquitin ligases that play a role in diverse processes from homeostasis and immune response to viral restriction. While TRIM proteins typically harbor an N-terminal RING finger, a B-box and a coiled-coil...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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International Union of Crystallography
2022-11-01
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| Series: | IUCrJ |
| Subjects: | |
| Online Access: | http://scripts.iucr.org/cgi-bin/paper?S2052252522008582 |
| _version_ | 1811244123017969664 |
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| author | Apirat Chaikuad Rezart Zhubi Claudia Tredup Stefan Knapp |
| author_facet | Apirat Chaikuad Rezart Zhubi Claudia Tredup Stefan Knapp |
| author_sort | Apirat Chaikuad |
| collection | DOAJ |
| description | Tripartite motif (TRIM) proteins constitute one of the largest subfamilies of the RING-type E3 ubiquitin ligases that play a role in diverse processes from homeostasis and immune response to viral restriction. While TRIM proteins typically harbor an N-terminal RING finger, a B-box and a coiled-coil domain, a high degree of diversity lies in their C termini that contain diverse protein interaction modules, most of which, both structures and their roles in intermolecular interactions, remain unknown. Here, high-resolution crystal structures of the NHL domains of three of the four human TRIM–NHL proteins, namely TRIM2, TRIM3 and TRIM71, are presented. Comparative structural analyses revealed that, despite sharing an evolutionarily conserved six-bladed β-propeller architecture, the low sequence identities resulted in distinct properties of these interaction domains at their putative binding sites for macromolecules. Interestingly, residues lining the binding cavities represent a hotspot for genetic mutations linked to several diseases. Thus, high sequence diversity within the conserved NHL domains might be essential for differentiating binding partners among TRIM–NHL proteins. |
| first_indexed | 2024-04-12T14:20:23Z |
| format | Article |
| id | doaj.art-0aee4b6a847f47998912754e7b217eae |
| institution | Directory Open Access Journal |
| issn | 2052-2525 |
| language | English |
| last_indexed | 2024-04-12T14:20:23Z |
| publishDate | 2022-11-01 |
| publisher | International Union of Crystallography |
| record_format | Article |
| series | IUCrJ |
| spelling | doaj.art-0aee4b6a847f47998912754e7b217eae2022-12-22T03:29:35ZengInternational Union of CrystallographyIUCrJ2052-25252022-11-019672072710.1107/S2052252522008582lz5059Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL familyApirat Chaikuad0Rezart Zhubi1Claudia Tredup2Stefan Knapp3Institute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, GermanyInstitute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, GermanyInstitute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, GermanyInstitute for Pharmaceutical Chemistry, Johann Wolfgang Goethe-University, Max-von-Laue-Strasse 9, D-60438 Frankfurt am Main, GermanyTripartite motif (TRIM) proteins constitute one of the largest subfamilies of the RING-type E3 ubiquitin ligases that play a role in diverse processes from homeostasis and immune response to viral restriction. While TRIM proteins typically harbor an N-terminal RING finger, a B-box and a coiled-coil domain, a high degree of diversity lies in their C termini that contain diverse protein interaction modules, most of which, both structures and their roles in intermolecular interactions, remain unknown. Here, high-resolution crystal structures of the NHL domains of three of the four human TRIM–NHL proteins, namely TRIM2, TRIM3 and TRIM71, are presented. Comparative structural analyses revealed that, despite sharing an evolutionarily conserved six-bladed β-propeller architecture, the low sequence identities resulted in distinct properties of these interaction domains at their putative binding sites for macromolecules. Interestingly, residues lining the binding cavities represent a hotspot for genetic mutations linked to several diseases. Thus, high sequence diversity within the conserved NHL domains might be essential for differentiating binding partners among TRIM–NHL proteins.http://scripts.iucr.org/cgi-bin/paper?S2052252522008582trim nhlsnhl domainstrim e3 ligasesprotein interaction domainsβ-propeller protein modulesgenetic mutations |
| spellingShingle | Apirat Chaikuad Rezart Zhubi Claudia Tredup Stefan Knapp Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family IUCrJ trim nhls nhl domains trim e3 ligases protein interaction domains β-propeller protein modules genetic mutations |
| title | Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family |
| title_full | Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family |
| title_fullStr | Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family |
| title_full_unstemmed | Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family |
| title_short | Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family |
| title_sort | comparative structural analyses of the nhl domains from the human e3 ligase trim nhl family |
| topic | trim nhls nhl domains trim e3 ligases protein interaction domains β-propeller protein modules genetic mutations |
| url | http://scripts.iucr.org/cgi-bin/paper?S2052252522008582 |
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