Medical College of Wisconsin
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Structural and agonist properties of XCL2, the other member of the C-chemokine subfamily. Cytokine 2015 Feb;71(2):302-11

Date

12/17/2014

Pubmed ID

25497737

Pubmed Central ID

PMC4297508

DOI

10.1016/j.cyto.2014.11.010

Scopus ID

2-s2.0-84916887047   19 Citations

Abstract

Known for its unusual metamorphic native state structure, XCL1 has been the focus of most efforts to elucidate the structural, functional, and physiological properties of chemokines in the C subfamily. By comparison, its closely related paralog XCL2 remains virtually uncharacterized. Based on the importance of the chemokine N-terminus in receptor activation, it was hypothesized that two amino acid differences in XCL2 would alter its agonist activity relative to XCL1 for their shared receptor XCR1. This present study reveals several properties of XCL2 that were unexamined until now. Structurally, XCL1 and XCL2 are very similar, exchanging between the monomeric chemokine fold and an unrelated dimeric state under physiological NaCl and temperature conditions. Ca(2+) flux, chemotaxis, and heparin binding assays showed that the monomer form of XCL2 is responsible for G protein-coupled receptor activation while the dimeric form is important for GAG binding. Despite their high structural similarity, XCL2 displays a slightly higher affinity for heparin than XCL1. Because their in vitro functional profiles are virtually identical, distinct physiological roles for XCL1 and XCL2 are probably encoded at the level of expression.

Author List

Fox JC, Nakayama T, Tyler RC, Sander TL, Yoshie O, Volkman BF

Author

Brian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Amino Acid Sequence
Animals
Calcium
Chemokines, C
Chemotaxis
Computational Biology
Heparin
Humans
Hydrogen-Ion Concentration
Kinetics
Lymphokines
Magnetic Resonance Spectroscopy
Molecular Sequence Data
Protein Binding
Protein Denaturation
Protein Multimerization
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Sialoglycoproteins
Signal Transduction
Sodium Chloride
Temperature
Thermodynamics
Urea
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