Exploring Chemokine Homodimer Stability: Structural Insights into CXC and CC Interfaces
Chemokine ligands play a pivotal role in immune response by mediating cell migration and coordinating cellular processes through interactions with chemokine receptors. Understanding their sequence and structural integrity is crucial for elucidating their biological functions and potential therapeuti...
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MDPI AG
2024-11-01
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| Series: | Biophysica |
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| Online Access: | https://www.mdpi.com/2673-4125/4/4/37 |
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| author | David Budean Yasser Almeida-Hernández Jitendra Pandey Joel Mieres Pérez Elsa Sánchez García Ellinor Haglund |
| author_facet | David Budean Yasser Almeida-Hernández Jitendra Pandey Joel Mieres Pérez Elsa Sánchez García Ellinor Haglund |
| author_sort | David Budean |
| collection | DOAJ |
| description | Chemokine ligands play a pivotal role in immune response by mediating cell migration and coordinating cellular processes through interactions with chemokine receptors. Understanding their sequence and structural integrity is crucial for elucidating their biological functions and potential therapeutic applications. In this study, we investigate the dimer interface between two distinct homodimer topologies: CXC and CC homodimers. Despite nearly identical monomeric structures, the rigid CXC interface is characterized by interactions between the N-loop/β-sheet regions, while the more flexible CC interface involves interactions through the unstructured N-terminal regions. Our structural and biophysical analyses indicate no significant differences in the free energy of folding (2–8 kcal/mol) and binding (10–14 kcal/mol) between the two homodimer topologies, showing that their free energy is primarily driven by sequence. We hypothesize that the biological signal is driven by the malleability of the dimer, depending on the binding interface. Understanding these structural dynamics opens new possibilities for designing chemokine-based therapeutics to modulate immune responses in diseases such as cancer, inflammation, and autoimmune disorders. |
| format | Article |
| id | doaj-art-dfb18a0621b74686b2ecf3d33f254933 |
| institution | OA Journals |
| issn | 2673-4125 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Biophysica |
| spelling | doaj-art-dfb18a0621b74686b2ecf3d33f2549332025-08-20T02:00:54ZengMDPI AGBiophysica2673-41252024-11-014456157210.3390/biophysica4040037Exploring Chemokine Homodimer Stability: Structural Insights into CXC and CC InterfacesDavid Budean0Yasser Almeida-Hernández1Jitendra Pandey2Joel Mieres Pérez3Elsa Sánchez García4Ellinor Haglund5Department of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USAFakultät für Bio- und Chemieingenieurwesen, Technische Universität Dortmund, Emil-Figge Str. 66, 44227 Dortmund, GermanyDepartment of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USAFakultät für Bio- und Chemieingenieurwesen, Technische Universität Dortmund, Emil-Figge Str. 66, 44227 Dortmund, GermanyFakultät für Bio- und Chemieingenieurwesen, Technische Universität Dortmund, Emil-Figge Str. 66, 44227 Dortmund, GermanyDepartment of Chemistry, University of Hawaii at Manoa, Honolulu, HI 96822, USAChemokine ligands play a pivotal role in immune response by mediating cell migration and coordinating cellular processes through interactions with chemokine receptors. Understanding their sequence and structural integrity is crucial for elucidating their biological functions and potential therapeutic applications. In this study, we investigate the dimer interface between two distinct homodimer topologies: CXC and CC homodimers. Despite nearly identical monomeric structures, the rigid CXC interface is characterized by interactions between the N-loop/β-sheet regions, while the more flexible CC interface involves interactions through the unstructured N-terminal regions. Our structural and biophysical analyses indicate no significant differences in the free energy of folding (2–8 kcal/mol) and binding (10–14 kcal/mol) between the two homodimer topologies, showing that their free energy is primarily driven by sequence. We hypothesize that the biological signal is driven by the malleability of the dimer, depending on the binding interface. Understanding these structural dynamics opens new possibilities for designing chemokine-based therapeutics to modulate immune responses in diseases such as cancer, inflammation, and autoimmune disorders.https://www.mdpi.com/2673-4125/4/4/37chemokineshomodimerdimer interfaceprotein–protein interactionconformational dynamicsprotein folding |
| spellingShingle | David Budean Yasser Almeida-Hernández Jitendra Pandey Joel Mieres Pérez Elsa Sánchez García Ellinor Haglund Exploring Chemokine Homodimer Stability: Structural Insights into CXC and CC Interfaces Biophysica chemokines homodimer dimer interface protein–protein interaction conformational dynamics protein folding |
| title | Exploring Chemokine Homodimer Stability: Structural Insights into CXC and CC Interfaces |
| title_full | Exploring Chemokine Homodimer Stability: Structural Insights into CXC and CC Interfaces |
| title_fullStr | Exploring Chemokine Homodimer Stability: Structural Insights into CXC and CC Interfaces |
| title_full_unstemmed | Exploring Chemokine Homodimer Stability: Structural Insights into CXC and CC Interfaces |
| title_short | Exploring Chemokine Homodimer Stability: Structural Insights into CXC and CC Interfaces |
| title_sort | exploring chemokine homodimer stability structural insights into cxc and cc interfaces |
| topic | chemokines homodimer dimer interface protein–protein interaction conformational dynamics protein folding |
| url | https://www.mdpi.com/2673-4125/4/4/37 |
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