Coiled-coil-domain-mediated TRIM E3 protein condensation modulates enzymatic activity and functional specificity
Summary: Tripartite motif (TRIM) proteins are E3 ligases with modular structures involved in diverse cellular functions. Whether biomolecular condensation broadly regulates TRIM proteins remains unclear. Here, we systematically examine 75 TRIMs in mammalian cells and find that the majority can form...
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Elsevier
2025-06-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725005376 |
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| author | Qi Chen Peiguo Yang |
| author_facet | Qi Chen Peiguo Yang |
| author_sort | Qi Chen |
| collection | DOAJ |
| description | Summary: Tripartite motif (TRIM) proteins are E3 ligases with modular structures involved in diverse cellular functions. Whether biomolecular condensation broadly regulates TRIM proteins remains unclear. Here, we systematically examine 75 TRIMs in mammalian cells and find that the majority can form condensates, either individually or together with other TRIMs. The coiled-coil (CC) domain is essential for TRIM condensation, and disease-related single-nucleotide polymorphisms (SNPs) in this domain impair condensate formation. We show that condensation modulates E3 ligase activity of several TRIMs in a context-dependent manner using cellular auto-ubiquitination and biotinylated-ubiquitination assays. Proteomic analysis reveals that proteins within 21 TRIM condensates are linked to key cellular pathways and diseases. Functional screening uncovers that certain TRIM condensates regulate centriolar satellite organization, cilia assembly, and microtubule stabilization. Our work provides foundational insights into the condensation and functions of TRIM family proteins and establishes a framework for studying co-condensation specificity among highly homologous proteins. |
| format | Article |
| id | doaj-art-bf7119fb74b34963bc14952a8dcf3796 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-bf7119fb74b34963bc14952a8dcf37962025-08-20T02:00:51ZengElsevierCell Reports2211-12472025-06-0144611576610.1016/j.celrep.2025.115766Coiled-coil-domain-mediated TRIM E3 protein condensation modulates enzymatic activity and functional specificityQi Chen0Peiguo Yang1College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, ChinaWestlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China; Corresponding authorSummary: Tripartite motif (TRIM) proteins are E3 ligases with modular structures involved in diverse cellular functions. Whether biomolecular condensation broadly regulates TRIM proteins remains unclear. Here, we systematically examine 75 TRIMs in mammalian cells and find that the majority can form condensates, either individually or together with other TRIMs. The coiled-coil (CC) domain is essential for TRIM condensation, and disease-related single-nucleotide polymorphisms (SNPs) in this domain impair condensate formation. We show that condensation modulates E3 ligase activity of several TRIMs in a context-dependent manner using cellular auto-ubiquitination and biotinylated-ubiquitination assays. Proteomic analysis reveals that proteins within 21 TRIM condensates are linked to key cellular pathways and diseases. Functional screening uncovers that certain TRIM condensates regulate centriolar satellite organization, cilia assembly, and microtubule stabilization. Our work provides foundational insights into the condensation and functions of TRIM family proteins and establishes a framework for studying co-condensation specificity among highly homologous proteins.http://www.sciencedirect.com/science/article/pii/S2211124725005376CP: Molecular biology |
| spellingShingle | Qi Chen Peiguo Yang Coiled-coil-domain-mediated TRIM E3 protein condensation modulates enzymatic activity and functional specificity Cell Reports CP: Molecular biology |
| title | Coiled-coil-domain-mediated TRIM E3 protein condensation modulates enzymatic activity and functional specificity |
| title_full | Coiled-coil-domain-mediated TRIM E3 protein condensation modulates enzymatic activity and functional specificity |
| title_fullStr | Coiled-coil-domain-mediated TRIM E3 protein condensation modulates enzymatic activity and functional specificity |
| title_full_unstemmed | Coiled-coil-domain-mediated TRIM E3 protein condensation modulates enzymatic activity and functional specificity |
| title_short | Coiled-coil-domain-mediated TRIM E3 protein condensation modulates enzymatic activity and functional specificity |
| title_sort | coiled coil domain mediated trim e3 protein condensation modulates enzymatic activity and functional specificity |
| topic | CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725005376 |
| work_keys_str_mv | AT qichen coiledcoildomainmediatedtrime3proteincondensationmodulatesenzymaticactivityandfunctionalspecificity AT peiguoyang coiledcoildomainmediatedtrime3proteincondensationmodulatesenzymaticactivityandfunctionalspecificity |