Academic Journal
CD44 enhances E-selectin-PSGL-1 interaction by binding to distinct sites on E-selectin.
| Τίτλος: | CD44 enhances E-selectin-PSGL-1 interaction by binding to distinct sites on E-selectin. |
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| Συγγραφείς: | Ding Q; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China., Wu Y; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Forensic Science and Technology, Criminal Investigation Police University of China, Shenyang, 110854, China., Li L; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; Key Laboratory of Biorheology Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, 400044, China., Zhang X; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China., Zheng Z; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China., Zhang M; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China., Zhang Y; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China., Long M; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: mlong@imech.ac.cn., Lü S; Center of Biomechanics and Bioengineering, Key Laboratory of Microgravity, and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing, 100190, China; School of Engineering Science, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: lsq@imech.ac.cn. |
| Πηγή: | International journal of biological macromolecules [Int J Biol Macromol] 2025 Dec; Vol. 333 (Pt 1), pp. 148825. Date of Electronic Publication: 2025 Nov 05. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: Guildford, Eng., IPC Science and Technology Press. |
| Ιατρικοί όροι (MeSH): | Hyaluronan Receptors*/metabolism , Hyaluronan Receptors*/chemistry , E-Selectin*/metabolism , E-Selectin*/chemistry , Membrane Glycoproteins*/metabolism , Membrane Glycoproteins*/chemistry, Humans ; Protein Binding ; Binding Sites ; Cell Adhesion ; Molecular Dynamics Simulation ; Ligands |
| Περίληψη: | Precise roles of E-selectin in inflammatory cascades, particularly concerning its primary ligands PSGL-1 and CD44, remain incompletely understood. Existing observations such as their co-localization, shared E-selectin-triggered signaling pathways, and cooperative contributions to cellular adhesion hint at a potential interplay of the ligands. We combined molecular simulations and experimental measurements to investigate the cooperative relationship between PSGL-1 and CD44 and elucidate the underlying structural mechanisms. Simulations predicted that CD44 binds to the hinge region between Lectin and EGF domains of E-selectin, spatially distinct from the PSGL-1 binding epitope located to the head interface of E-selectin Lectin domain. This spatial arrangement allowed for simultaneous binding of both PSGL-1 and CD44 to the same E-selectin molecule, and CD44 binding was predicted to enhance E-selectin-PSGL-1 interaction. Experimental validation upon flow chamber assay exhibited that adhesion of both PSGL-1 and CD44-coated microbead to E-selectin-coated substrate was significantly higher than either ligand-coated alone, even at comparable coating densities. Moreover, both atomic force microscopy and acoustic force spectroscopy assays demonstrated that the binding strength of E-selectin-PSGL-1 interaction increased in the presence of soluble CD44. Co-localization of PSGL-1 and CD44, the precondition for binding cooperatively to the same E-selectin molecule, was also confirmed on both HL-60 and primary PMN cells using Immunofluorescence assay. These findings provided a more comprehensive understanding in differential roles and underling mechanisms of E-selectin-ligand interactions in immune responses. (Copyright © 2025 Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Cellular adhesion; E-selectin; Ligand cooperation |
| Substance Nomenclature: | 0 (Hyaluronan Receptors) 0 (E-Selectin) 0 (P-selectin ligand protein) 0 (Membrane Glycoproteins) 0 (CD44 protein, human) 0 (Ligands) |
| Entry Date(s): | Date Created: 20251107 Date Completed: 20251202 Latest Revision: 20251202 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.ijbiomac.2025.148825 |
| PMID: | 41203159 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1879-0003 |
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| DOI: | 10.1016/j.ijbiomac.2025.148825 |