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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634614/ https://www.ncbi.nlm.nih.gov/pubmed/36381143 http://dx.doi.org/10.1107/S2052252522008582 |
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author | Chaikuad, Apirat Zhubi, Rezart Tredup, Claudia Knapp, Stefan |
author_facet | Chaikuad, Apirat Zhubi, Rezart Tredup, Claudia Knapp, Stefan |
author_sort | Chaikuad, Apirat |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-9634614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-96346142022-11-14 Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family Chaikuad, Apirat Zhubi, Rezart Tredup, Claudia Knapp, Stefan IUCrJ Research Letters 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. International Union of Crystallography 2022-09-27 /pmc/articles/PMC9634614/ /pubmed/36381143 http://dx.doi.org/10.1107/S2052252522008582 Text en © Apirat Chaikuad et al. 2022 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited. |
spellingShingle | Research Letters Chaikuad, Apirat Zhubi, Rezart Tredup, Claudia Knapp, Stefan Comparative structural analyses of the NHL domains from the human E3 ligase TRIM–NHL family |
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 | Research Letters |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634614/ https://www.ncbi.nlm.nih.gov/pubmed/36381143 http://dx.doi.org/10.1107/S2052252522008582 |
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