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Title: NMR characterization of cooperativity: fast ligand binding coupled to slow protein dimerization
Contributor(s): Huma, Zil E (author); Ludeman, Justin P (author); Wilkinson, Brendan  (author)orcid ; Payne, Richard J (author); Stone, Martin J (author)
Publication Date: 2014
Open Access: Yes
DOI: 10.1039/c4sc00131aOpen Access Link
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Abstract: We describe a general approach for analysis of 2D NMR spectra to evaluate the cooperativity of ligand binding and protein dimerization in coupled systems. The approach is applicable to systems in which NMR spectra display separate resonances for monomeric and dimeric species but each resonance shifts in response to ligand binding. Three experimental parameters (monomer chemical shift, dimer chemical shift and relative monomer-dimer peak intensity) are fitted globally, as a function of ligand concentration, to yield equilibrium constants for dimerization, monomer-ligand binding and dimer-ligand binding as well as the cooperativity between ligand binding and dimerization. We have applied the approach to characterise a system in which dimerization of the chemokine monocyte chemoattractant protein-1 (MCP-1/CCL2) is coupled to binding of peptides derived from the chemokine receptor CCR2. The global fitting approach allowed evaluation of cooperativity with higher precision than is possible by alternative methods.
Publication Type: Journal Article
Grant Details: ARC/DE130101673
Source of Publication: Chemical Science, 5(7), p. 2783-2788
Publisher: Royal Society of Chemistry
Place of Publication: United Kingdom
ISSN: 2041-6520
Field of Research (FOR): 030403 Characterisation of Biological Macromolecules
030406 Proteins and Peptides
030402 Biomolecular Modelling and Design
Socio-Economic Outcome Codes: 970103 Expanding Knowledge in the Chemical Sciences
929999 Health not elsewhere classified
970106 Expanding Knowledge in the Biological Sciences
Peer Reviewed: Yes
HERDC Category Description: C1 Refereed Article in a Scholarly Journal
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