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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/CXCL2_MOUSE CXCL2_MOUSE] Chemotactic for human polymorphonuclear leukocytes but does not induce chemokinesis or an oxidative burst. | [https://www.uniprot.org/uniprot/CXCL2_MOUSE CXCL2_MOUSE] Chemotactic for human polymorphonuclear leukocytes but does not induce chemokinesis or an oxidative burst. | ||
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== Publication Abstract from PubMed == | |||
MIP-2/CXCL2 is a murine chemokine related to human chemokines that possesses the Glu-Leu-Arg (ELR) activation motif and activates CXCR2 for neutrophil chemotaxis. We determined the structure of MIP-2 to 1.9 A resolution and created a model with its murine receptor CXCR2 based on the coordinates of human CXCR4. Chemokine-induced migration of cells through specific G-protein coupled receptors is regulated by glycosaminoglycans (GAGs) that oligomerize chemokines. MIP-2 GAG-binding residues were identified that interact with heparin disaccharide I-S by NMR spectroscopy. A model GAG/MIP-2/CXCR2 complex that supports a 2:2 complex between chemokine and receptor was created. Mutants of these disaccharide-binding residues were made and tested for heparin binding, in vitro neutrophil chemotaxis, and in vivo neutrophil recruitment to the mouse peritoneum and lung. The mutants have a 10-fold decrease in neutrophil chemotaxis in vitro. There is no difference in neutrophil recruitment between wild-type MIP-2 and mutants in the peritoneum, but all activity of the mutants is lost in the lung, supporting the concept that GAG regulation of chemokines is tissue-dependent. | |||
A Model of GAG/MIP-2/CXCR2 Interfaces and Its Functional Effects.,Rajasekaran D, Keeler C, Syed MA, Jones MC, Harrison JK, Wu D, Bhandari V, Hodsdon ME, Lolis EJ Biochemistry. 2012 Jul 2. PMID:22686371<ref>PMID:22686371</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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==See Also== | ==See Also== | ||
*[[C-X-C motif chemokine 3D structures|C-X-C motif chemokine 3D structures]] | *[[C-X-C motif chemokine 3D structures|C-X-C motif chemokine 3D structures]] | ||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> |