Dissecting the differential structural and dynamics features of CCL2 chemokine orthologs.
Amino Acid Sequence
Animals
Binding Sites
Chemokine CCL2
/ chemistry
Chemokines
/ chemistry
Cloning, Molecular
Evolution, Molecular
Gene Expression
Magnetic Resonance Spectroscopy
Mice
Models, Molecular
Phylogeny
Protein Binding
Protein Conformation
Protein Multimerization
Recombinant Proteins
Spectrum Analysis
Structure-Activity Relationship
Chemokines
G-protein coupled receptor (GPCR)
Glycosaminoglycans (GAGs)
Molecular evolution
Nuclear magnetic resonance (NMR)
Journal
International journal of biological macromolecules
ISSN: 1879-0003
Titre abrégé: Int J Biol Macromol
Pays: Netherlands
ID NLM: 7909578
Informations de publication
Date de publication:
01 Aug 2020
01 Aug 2020
Historique:
received:
26
12
2019
revised:
26
03
2020
accepted:
08
04
2020
pubmed:
15
4
2020
medline:
11
3
2021
entrez:
15
4
2020
Statut:
ppublish
Résumé
Chemokines are a sub-group of cytokines that regulate the leukocyte migration. Monocyte chemoattractant protein-1 (MCP/CCL2) is one of the essential CC chemokine that regulates the migration of monocytes into inflamed tissues. It has been observed that the primary sequences of CCL2 orthologs among rodents and primates vary significantly at the C-terminal region. However, no structural details are available for the rodentia family CCL2 proteins. The current study unravelled the structural, dynamics and in-silico functional characteristics of murine CCL2 chemokine using a comprehensive set of NMR spectroscopy techniques and evolutionary approaches. The study unravelled that the N-terminal portion of the murine CCL2 forms a canonical CC chemokine dimer similar to that of human CCL2. However, unlike human CCL2, the murine ortholog exhibits extensive dynamics in the μs-ms timescales. The presence of C-terminal region of the murine CCL2 protein/rodentia family is highly glycosylated, completely disordered, and inhibits the folding of the structured CCL2 regions. Further, it has been observed that the glycosaminoglycan binding surfaces of these orthologs proteins are greatly differed. In a nut shell, this comparative study provided the role of molecular evolution in generating orthologous proteins with differential structural and dynamics characteristics to engage them in specific molecular interactions.
Identifiants
pubmed: 32289428
pii: S0141-8130(20)32923-8
doi: 10.1016/j.ijbiomac.2020.04.067
pii:
doi:
Substances chimiques
Chemokine CCL2
0
Chemokines
0
Recombinant Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
239-251Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.