3N52

crystal Structure analysis of MIP2

Summary for 3N52

• Entry DOI: 10.2210/pdb3n52/pdb
• Descriptor: C-X-C motif chemokine 2 (2 entities in total)
• Functional Keywords: mip-2 structure, macrophage inflammatory protein 2, cxcl2, cytokine
• Biological source: Mus musculus (mouse)
• Cellular location: Secreted: P10889
• Total number of polymer chains: 4
• Total formula weight: 31441.24

Authors

Rajasekaran, D. (deposition date: 2010-05-24, release date: 2011-06-08, Last modification date: 2024-11-27)

Primary citation

Rajasekaran, D.,Keeler, C.,Syed, M.A.,Jones, M.C.,Harrison, J.K.,Wu, D.,Bhandari, V.,Hodsdon, M.E.,Lolis, E.J.
A Model of GAG/MIP-2/CXCR2 Interfaces and Its Functional Effects.
Biochemistry, 51:5642-5654, 2012

PubMed Abstract: 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 Å 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.

PubMed: 22686371
DOI: 10.1021/bi3001566

Experimental method

X-RAY DIFFRACTION (1.9 Å)