Document Detail


Differentiation of CC vs CXC chemokine dimers with GAG octasaccharide binding partners: an ion mobility mass spectrometry approach.
MedLine Citation:
PMID:  23418647     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chemokines, 8 kDa proteins implicated in leukocyte migration via oligomerization, bind to glycosaminoglycans (GAGs) during the inflammation response as a means to regulate chemokine migration. Structural characterization of chemokines non-covalently bound to GAGs provides physiologically meaningful data in regard to routine inmmunosurveillance and disease response. In order to analyze the structures resulting from the GAG:chemokine interaction, we employed ion mobility mass spectrometry (IMMS) to analyze monocyte chemoattractant protein-1 (MCP-1), a CC chemokine, and interleukin-8 (IL-8), a CXC chemokine, along with their individual interactions with GAG heparin octasaccharides. We show that MCP-1 and IL-8 are physiologically present as a dimer, with MCP-1 having two variants of its dimeric form and IL-8 having only one. We also show that the MCP-1 dimer adopts two conformations, one extended and one compact, when bound to a dodecasulfated heparin octasaccharide. Binding of MCP-1 to heparin octasaccharide isomers of varying sulfation patterns results in similar arrival time distribution values, which suggests minimal distinguishing features among the resultant complexes. Additionally, tandem mass spectrometry (MS/MS) showed that the binding of MCP-1 to a heparin octasaccharide has different dissociation patterns when compared with the corresponding IL-8 bound dimer. Overall, IMMS and MS/MS were used to better define the structural tendencies and differences associated with CC and CXC dimers when associated with GAG octasaccharides.
Authors:
Youjin Seo; Armann Andaya; Christian Bleiholder; Julie A Leary
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-03-07
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  135     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-20     Completed Date:  2013-09-09     Revised Date:  2014-05-13    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4325-32     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Chemokine CCL2 / chemistry,  metabolism*
Heparin / chemistry,  metabolism*
Humans
Interleukin-8 / chemistry,  metabolism*
Models, Molecular
Protein Binding
Protein Conformation
Protein Multimerization
Tandem Mass Spectrometry
Grant Support
ID/Acronym/Agency:
GM47356/GM/NIGMS NIH HHS; R01 GM047356/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Chemokine CCL2; 0/Interleukin-8; 9005-49-6/Heparin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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