Dissecting the differential structural and dynamics features of CCL2 chemokine orthologs.


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
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

239-251

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Auteurs

Nidhi Joshi (N)

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

Nupur Nagar (N)

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

Khushboo Gulati (K)

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

Krishnakant Gangele (K)

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India.

Amit Mishra (A)

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur 342037, Rajasthan, India.

Dinesh Kumar (D)

Centre of Biomedical Research, SGPGIMS Campus, Lucknow 226014, Uttar Pradesh, India.

Krishna Mohan Poluri (KM)

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, Uttarakhand, India. Electronic address: krishfbt@iitr.ac.in.

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Classifications MeSH