Chemokines and their receptors: insights from molecular modeling and crystallography

Curr Opin Pharmacol. 2016 Oct;30:27-37. doi: 10.1016/j.coph.2016.07.006. Epub 2016 Jul 25.


Chemokines are small secreted proteins that direct cell migration in development, immunity, inflammation, and cancer. They do so by binding and activating specific G protein coupled receptors on the surface of migrating cells. Despite the importance of receptor:chemokine interactions, their structural basis remained unclear for a long time. In 2015, the first atomic resolution insights were obtained with the publication of X-ray structures for two distantly related receptors bound to chemokines. In conjunction with experiment-guided molecular modeling, the structures suggest a conserved receptor:chemokine complex architecture, while highlighting the diverse details and functional roles of individual interaction epitopes. Novel findings promote the development and detailed structural interpretation of the canonical two-site hypothesis of receptor:chemokine recognition, and suggest new avenues for pharmacological modulation of chemokine receptors.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Movement
  • Chemokines / metabolism*
  • Crystallography
  • Humans
  • Models, Molecular*
  • Receptors, Chemokine / chemistry
  • Receptors, Chemokine / metabolism*
  • Receptors, G-Protein-Coupled / metabolism


  • Chemokines
  • Receptors, Chemokine
  • Receptors, G-Protein-Coupled