Cysteine residues are critical for chemokine receptor CXCR2 functional properties

Cristina Limatola, Sabrina Di Bartolomeo, Myriam Catalano, Flavia Trettel, Sergio Fucile, Loriana Castellani, Fabrizio Eusebi

Research output: Contribution to journalArticle


We examined the role of cysteine (Cys) residues present in chemokine receptor CXCR2 for proper surface expression, dimerization, signaling, and chemotaxis. To address this issue, serine or leucine residues were substituted for Cys, generating nine CXCR2 mutants transiently expressed in HEK cells. Single substitution of Cys residues present in the three extracellular loops (C119L, C196L, C286S) or in the seventh-transmembrane (TM) domain (C308L) abolished CXCL8 agonist binding, while no Cys substitution abolished surface receptor expression. We have previously demonstrated that CXCR2 dimerizes under reducing conditions, due to hydrophobic interactions that involve TM3 regions, and here we show that the dimer/monomer CXCR2 ratio drastically increases when analyzed under non-reducing conditions. We report that none of the Cys-deficient CXCR2 mutants abolishes receptor dimerization, demonstrating that Cys-Cys bonds are not the exclusive determinant of CXCR2 dimerization. Furthermore, both wt- and Cys-mutated CXCR2 dimers are expressed at the cell surface, indicating that receptor dimers are efficiently transferred at the plasma membrane. We also show that every Cys substitution in CXCR2, including those that still bind CXCL8, results in an impairment of receptor activity, analyzed as cell chemotaxis and intracellular signaling, suggesting that some structural requirement is likely fulfilled by Cys presence.

Original languageEnglish
Pages (from-to)65-75
Number of pages11
JournalExperimental Cell Research
Issue number1
Publication statusPublished - Jul 1 2005


  • Chemotaxis
  • CXCR2
  • Cysteines
  • Receptor dimerization
  • Signal transduction

ASJC Scopus subject areas

  • Cell Biology

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