UXT oligomerization is essential for its role as an autophagy adaptor
Summary: SQSTM1/p62 serves as an autophagy receptor that binds to ubiquitinated misfolded proteins and delivers them to the phagophores for removal. This function can be augmented by autophagy adaptors, such as UXT. Here, by in silico structural homology modeling, we demonstrated that UXT can potent...
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| Language: | English |
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Elsevier
2025-03-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225002731 |
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| author | Min Ji Yoon Jugeon Park MinHyeong Lee Jiyeon Ohk Tae Su Choi Eun Jung Choi Hosung Jung Chungho Kim |
| author_facet | Min Ji Yoon Jugeon Park MinHyeong Lee Jiyeon Ohk Tae Su Choi Eun Jung Choi Hosung Jung Chungho Kim |
| author_sort | Min Ji Yoon |
| collection | DOAJ |
| description | Summary: SQSTM1/p62 serves as an autophagy receptor that binds to ubiquitinated misfolded proteins and delivers them to the phagophores for removal. This function can be augmented by autophagy adaptors, such as UXT. Here, by in silico structural homology modeling, we demonstrated that UXT can potentially form a hexameric structure to bind to misfolded proteins. Importantly, the UXT hexamer can assemble into a high-order oligomer via β hairpins positioned outside of each hexamer, facilitating the formation and efficient removal of protein aggregates. Consistently, the high-order oligomer of UXT was found to be essential for inducing the efficient clearance of SOD1(A4V) aggregates, in both in vitro and in vivo. Collectively, our research emphasizes the crucial importance of UXT oligomerization in its role as an autophagy adaptor and explains why the structurally and functionally similar prefoldin, which lacks such high-order oligomerization capacity, is employed for the refolding of individual misfolded proteins, but not autophagy. |
| format | Article |
| id | doaj-art-cd048f28638b404a9841f1c3ef1f4865 |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-cd048f28638b404a9841f1c3ef1f48652025-08-20T03:04:38ZengElsevieriScience2589-00422025-03-0128311201310.1016/j.isci.2025.112013UXT oligomerization is essential for its role as an autophagy adaptorMin Ji Yoon0Jugeon Park1MinHyeong Lee2Jiyeon Ohk3Tae Su Choi4Eun Jung Choi5Hosung Jung6Chungho Kim7Department of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of KoreaDepartment of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of KoreaPotomac Affinity Proteins, 11305 Dunleith Pl, North Potomac, MD 20878, USADepartment of Anatomy, Graduate School of Medical Science, Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDepartment of Life Sciences, Korea University, Seoul 02841, Republic of Korea; Corresponding authorSummary: SQSTM1/p62 serves as an autophagy receptor that binds to ubiquitinated misfolded proteins and delivers them to the phagophores for removal. This function can be augmented by autophagy adaptors, such as UXT. Here, by in silico structural homology modeling, we demonstrated that UXT can potentially form a hexameric structure to bind to misfolded proteins. Importantly, the UXT hexamer can assemble into a high-order oligomer via β hairpins positioned outside of each hexamer, facilitating the formation and efficient removal of protein aggregates. Consistently, the high-order oligomer of UXT was found to be essential for inducing the efficient clearance of SOD1(A4V) aggregates, in both in vitro and in vivo. Collectively, our research emphasizes the crucial importance of UXT oligomerization in its role as an autophagy adaptor and explains why the structurally and functionally similar prefoldin, which lacks such high-order oligomerization capacity, is employed for the refolding of individual misfolded proteins, but not autophagy.http://www.sciencedirect.com/science/article/pii/S2589004225002731BiochemistryMolecular biology |
| spellingShingle | Min Ji Yoon Jugeon Park MinHyeong Lee Jiyeon Ohk Tae Su Choi Eun Jung Choi Hosung Jung Chungho Kim UXT oligomerization is essential for its role as an autophagy adaptor iScience Biochemistry Molecular biology |
| title | UXT oligomerization is essential for its role as an autophagy adaptor |
| title_full | UXT oligomerization is essential for its role as an autophagy adaptor |
| title_fullStr | UXT oligomerization is essential for its role as an autophagy adaptor |
| title_full_unstemmed | UXT oligomerization is essential for its role as an autophagy adaptor |
| title_short | UXT oligomerization is essential for its role as an autophagy adaptor |
| title_sort | uxt oligomerization is essential for its role as an autophagy adaptor |
| topic | Biochemistry Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225002731 |
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