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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...

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Autores principales: Chaikuad, Apirat, Zhubi, Rezart, Tredup, Claudia, Knapp, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2022
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.
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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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