Filamentous chemokine CCL5 structure and the functional aspects
Abstract Human inflammation-related CC chemokine ligand 5 (hCCL5) has significant self-assembly property under physiological conditions. The mechanism and function of hCCL5 oligomerization remain unclear. Different intermolecular interactions, such as E66-K25 or E66-R44/K45, have been reported to me...
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Nature Portfolio
2025-04-01
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| Online Access: | https://doi.org/10.1038/s41598-025-98114-9 |
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| author | Yi-Ting Yuan Tzu-Ching Guo Chu-Ya Wu Yi-Qi Yeh Ching‑Tse Wu Shu-Yao Hsu Zi-Wen Weng Meng-Ru Ho Shang-Te Danny Hsu Yi-Chen Chen Chuang‑Rung Chang Kuen-Phon Wu U-Ser Jeng Shih-Che Sue |
| author_facet | Yi-Ting Yuan Tzu-Ching Guo Chu-Ya Wu Yi-Qi Yeh Ching‑Tse Wu Shu-Yao Hsu Zi-Wen Weng Meng-Ru Ho Shang-Te Danny Hsu Yi-Chen Chen Chuang‑Rung Chang Kuen-Phon Wu U-Ser Jeng Shih-Che Sue |
| author_sort | Yi-Ting Yuan |
| collection | DOAJ |
| description | Abstract Human inflammation-related CC chemokine ligand 5 (hCCL5) has significant self-assembly property under physiological conditions. The mechanism and function of hCCL5 oligomerization remain unclear. Different intermolecular interactions, such as E66-K25 or E66-R44/K45, have been reported to mediate hCCL5 oligomerization. This complexity makes structural determination difficult. Based on a K25S mutation to eliminate the E66-K25 interaction, we observed hCCL5 forming a helical-sharped filament in transmission electron microscopy (TEM). The filamentous polymerization is a dominant process when the concentration reaches ~ 100 nM and the filaments further form a higher-order assembly when concentration increases. In this large filament, a combination of X-ray solution scattering and cryo-EM analysis determined the structure; NMR further confirmed the filament packing, in which the interactions of residues R44 and K45 are critically involved. The sequence 43TRKNR47 was found to be essential for CCL5 trafficking inside the cells and for glycosaminoglycan binding outside the cells. The functional aspects of the chemokine filament are discussed. |
| format | Article |
| id | doaj-art-4241bb51bf224e7099a6d07bde03a5b6 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4241bb51bf224e7099a6d07bde03a5b62025-08-20T02:24:29ZengNature PortfolioScientific Reports2045-23222025-04-0115111310.1038/s41598-025-98114-9Filamentous chemokine CCL5 structure and the functional aspectsYi-Ting Yuan0Tzu-Ching Guo1Chu-Ya Wu2Yi-Qi Yeh3Ching‑Tse Wu4Shu-Yao Hsu5Zi-Wen Weng6Meng-Ru Ho7Shang-Te Danny Hsu8Yi-Chen Chen9Chuang‑Rung Chang10Kuen-Phon Wu11U-Ser Jeng12Shih-Che Sue13Institute of Bioinformatics and Structural Biology, National Tsing Hua UniversityInstitute of Bioinformatics and Structural Biology, National Tsing Hua UniversityInstrumentation Center, National Tsing Hua UniversityNational Synchrotron Radiation Research CenterInstitute of Biotechnology, National Tsing Hua UniversityInstitute of Biotechnology, National Tsing Hua UniversityInstitute of Biological Chemistry, Academia SinicaInstitute of Biological Chemistry, Academia SinicaInstitute of Biological Chemistry, Academia SinicaInstitute of Bioinformatics and Structural Biology, National Tsing Hua UniversityInstitute of Biotechnology, National Tsing Hua UniversityInstitute of Biological Chemistry, Academia SinicaDepartment of Chemical Engineering, National Tsing Hua UniversityInstitute of Bioinformatics and Structural Biology, National Tsing Hua UniversityAbstract Human inflammation-related CC chemokine ligand 5 (hCCL5) has significant self-assembly property under physiological conditions. The mechanism and function of hCCL5 oligomerization remain unclear. Different intermolecular interactions, such as E66-K25 or E66-R44/K45, have been reported to mediate hCCL5 oligomerization. This complexity makes structural determination difficult. Based on a K25S mutation to eliminate the E66-K25 interaction, we observed hCCL5 forming a helical-sharped filament in transmission electron microscopy (TEM). The filamentous polymerization is a dominant process when the concentration reaches ~ 100 nM and the filaments further form a higher-order assembly when concentration increases. In this large filament, a combination of X-ray solution scattering and cryo-EM analysis determined the structure; NMR further confirmed the filament packing, in which the interactions of residues R44 and K45 are critically involved. The sequence 43TRKNR47 was found to be essential for CCL5 trafficking inside the cells and for glycosaminoglycan binding outside the cells. The functional aspects of the chemokine filament are discussed.https://doi.org/10.1038/s41598-025-98114-9Chemokine CCL5Filamentcryo-EMSWAXSNMRChemokine secretion |
| spellingShingle | Yi-Ting Yuan Tzu-Ching Guo Chu-Ya Wu Yi-Qi Yeh Ching‑Tse Wu Shu-Yao Hsu Zi-Wen Weng Meng-Ru Ho Shang-Te Danny Hsu Yi-Chen Chen Chuang‑Rung Chang Kuen-Phon Wu U-Ser Jeng Shih-Che Sue Filamentous chemokine CCL5 structure and the functional aspects Scientific Reports Chemokine CCL5 Filament cryo-EM SWAXS NMR Chemokine secretion |
| title | Filamentous chemokine CCL5 structure and the functional aspects |
| title_full | Filamentous chemokine CCL5 structure and the functional aspects |
| title_fullStr | Filamentous chemokine CCL5 structure and the functional aspects |
| title_full_unstemmed | Filamentous chemokine CCL5 structure and the functional aspects |
| title_short | Filamentous chemokine CCL5 structure and the functional aspects |
| title_sort | filamentous chemokine ccl5 structure and the functional aspects |
| topic | Chemokine CCL5 Filament cryo-EM SWAXS NMR Chemokine secretion |
| url | https://doi.org/10.1038/s41598-025-98114-9 |
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