Structural biology of chemokine receptors

Daniel Rojo, Katsutoshi Suetomi, Javier Navarro

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Chemokine receptors are G protein-coupled receptors that mediate migration and activation of leukocytes as an important part of a protective immune response to injury and infection. In addition, chemokine receptors are used by HIV-1 to infect CD4 positive cells. The structural bases of chemokine receptor recognition and signal transduction are currently being investigated. High-resolution X-ray diffraction and NMR spectroscopy of chemokines indicate that all these peptides exhibit a common folding pattern, in spite of its low degree of primary sequence homology. Chemokines' functional motifs have been identified by mutagenesis studies, and a possible mechanism for receptor recognition and activation is proposed, but high-resolution structure data of chemokine receptors is not yet available. Studies with receptor chimeras have identified the putative extracellular domains as the major selectivity determinants. Single-amino acid substitutions in the extracellular domains produce profound changes in receptor specificity, suggesting that motifs in these domains operate as a restrictive barrier to a common activation motif. Similarly HIV-1 usage of chemokine receptors involves interaction of one or more extracellular domains of the receptor with conserved and variable domains on the viral envelope protein gp 120, indicating a highly complex interaction. Elucidating the structural requirements for receptor interaction with chemokines and with HIV-1 will provide important insights into understanding the mechanisms of chemokine recognition and receptor activation. In addition, this information can greatly facilitate the design of effective inmunomodulatory and anti-HIV-1 therapeutic agents.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalBiological Research
Volume32
Issue number4
StatePublished - 1999

Fingerprint

Chemokine Receptors
Chemokines
chemokines
Human immunodeficiency virus 1
Biological Sciences
receptors
Chemical activation
HIV-1
Viral Envelope Proteins
Signal transduction
Mutagenesis
G-Protein-Coupled Receptors
chimerism
Nuclear magnetic resonance spectroscopy
amino acid substitution
Amino Acid Substitution
Sequence Homology
sequence homology
mutagenesis
X-ray diffraction

Keywords

  • Chemokines
  • G-protein coupled receptors
  • HIV-1
  • Inflammation

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Rojo, D., Suetomi, K., & Navarro, J. (1999). Structural biology of chemokine receptors. Biological Research, 32(4), 263-272.

Structural biology of chemokine receptors. / Rojo, Daniel; Suetomi, Katsutoshi; Navarro, Javier.

In: Biological Research, Vol. 32, No. 4, 1999, p. 263-272.

Research output: Contribution to journalArticle

Rojo, D, Suetomi, K & Navarro, J 1999, 'Structural biology of chemokine receptors', Biological Research, vol. 32, no. 4, pp. 263-272.
Rojo, Daniel ; Suetomi, Katsutoshi ; Navarro, Javier. / Structural biology of chemokine receptors. In: Biological Research. 1999 ; Vol. 32, No. 4. pp. 263-272.
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