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250714s2025 xx |||||o 00| ||eng c |
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|a 10.1002/mrc.70016
|2 doi
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|a pubmed25n1552.xml
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|e rakwb
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| 041 |
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|a eng
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| 100 |
1 |
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|a Tripathi, Deepak Kumar
|e verfasserin
|4 aut
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| 245 |
1 |
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|a NMR Elucidation of Structure-Dynamics-Function Relationship of Engineered CCL2 Chemokine Monomer
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|c 2025
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
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|2 rdacarrier
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|a Date Completed 01.09.2025
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|a Date Revised 01.09.2025
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2025 John Wiley & Sons Ltd.
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|a The monocyte migration at the inflammatory site is regulated by monocyte chemoattractant protein-1 (MCP/CCL2), a crucial CC chemokine existing in equilibrium between monomers and dimers under physiological conditions. The present study unveils the relative structure-stability and functional features for engineered murine CCL2-P8A monomer (CCL2-M) in comparison to dimer (CCL2-WT) using a combination of nuclear magnetic resonance (NMR), biophysical and cell-based techniques. We delineate here the NMR assignment and structural characteristics of wild-type and monomeric versions of CCL2 protein. The structural features revealed that the overall topology of the CCL2-M is similar to that of the monomeric subunit of the CCL2-WT protein. The conformational dynamics of CCL2-M exhibit extensive fluctuations in the μs-ms timescales, with fewer residues accessing alternative conformations than CCL2 dimer, indicating differential native state ruggedness of the monomer. Native state hydrogen exchange analysis shows that most residues in the CCL2 monomer are readily accessible to solvent and exchangeable, suggesting lower stability of the CCL2 monomer than the dimer. Cell-based transwell migration assay demonstrates that CCL2 monomer induces chemotactic migration of monocyte/macrophages similar to its dimeric counterpart. These investigations align closely with the structural-functional aspects of CCL2 and form the basis for the structure-based drug discovery targeting its cognate G-protein coupled receptor CCR2
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|a Journal Article
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|a chemokines
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| 650 |
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|a leukocyte recruitment
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| 650 |
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4 |
|a monocyte chemoattractant protein
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| 650 |
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4 |
|a nuclear magnetic resonance spectroscopy
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| 650 |
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4 |
|a protein engineering
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| 650 |
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|a Chemokine CCL2
|2 NLM
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| 650 |
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|a Ccl2 protein, mouse
|2 NLM
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| 700 |
1 |
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|a Gulati, Khushboo
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Pramanik, Siddhartha Das
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Roy, Partha
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Kumar, Dinesh
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Poluri, Krishna Mohan
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Magnetic resonance in chemistry : MRC
|d 1985
|g 63(2025), 10 vom: 12. Sept., Seite 784-795
|w (DE-627)NLM098179667
|x 1097-458X
|7 nnas
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| 773 |
1 |
8 |
|g volume:63
|g year:2025
|g number:10
|g day:12
|g month:09
|g pages:784-795
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|u http://dx.doi.org/10.1002/mrc.70016
|3 Volltext
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