PMID- 23418647
OWN - NLM
STAT- MEDLINE
DCOM- 20130909
LR  - 20211021
IS  - 1520-5126 (Electronic)
IS  - 0002-7863 (Linking)
VI  - 135
IP  - 11
DP  - 2013 Mar 20
TI  - Differentiation of CC vs CXC chemokine dimers with GAG octasaccharide binding 
      partners: an ion mobility mass spectrometry approach.
PG  - 4325-32
LID - 10.1021/ja310915m [doi]
AB  - 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.
FAU - Seo, Youjin
AU  - Seo Y
AD  - Department of Chemistry, University of California, Davis, California 95616, USA.
FAU - Andaya, Armann
AU  - Andaya A
FAU - Bleiholder, Christian
AU  - Bleiholder C
FAU - Leary, Julie A
AU  - Leary JA
LA  - eng
GR  - R01 GM047356/GM/NIGMS NIH HHS/United States
GR  - GM47356/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130307
PL  - United States
TA  - J Am Chem Soc
JT  - Journal of the American Chemical Society
JID - 7503056
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Chemokine CCL2/chemistry/*metabolism
MH  - Heparin/chemistry/*metabolism
MH  - Humans
MH  - Interleukin-8/chemistry/*metabolism
MH  - Models, Molecular
MH  - Protein Binding
MH  - Protein Conformation
MH  - Protein Multimerization
MH  - Tandem Mass Spectrometry
EDAT- 2013/02/20 06:00
MHDA- 2013/09/10 06:00
CRDT- 2013/02/20 06:00
PHST- 2013/02/20 06:00 [entrez]
PHST- 2013/02/20 06:00 [pubmed]
PHST- 2013/09/10 06:00 [medline]
AID - 10.1021/ja310915m [doi]
PST - ppublish
SO  - J Am Chem Soc. 2013 Mar 20;135(11):4325-32. doi: 10.1021/ja310915m. Epub 2013 Mar 
      7.