Supplementary Materials

Supplementary Materials for:

Structural basis for chemokine recognition by a G protein–coupled receptor and implications for receptor activation

Joshua J. Ziarek, Andrew B. Kleist, Nir London, Barak Raveh, Nicolas Montpas, Julien Bonneterre, Geneviève St-Onge, Crystal J. DiCosmo-Ponticello, Chad A. Koplinski, Ishan Roy, Bryan Stephens, Sylvia Thelen, Christopher T. Veldkamp, Frederick D. Coffman, Marion C. Cohen, Michael B. Dwinell, Marcus Thelen, Francis C. Peterson, Nikolaus Heveker, Brian F. Volkman*

*Corresponding author. Email: bvolkman{at}

This PDF file includes:

  • Methods
  • Fig. S1. Stereo images of the LM:CXCR41–38 NMR ensemble containing 20 individual structures.
  • Fig. S2. The LM CXCL12 variant is incapable of CXC-type dimerization.
  • Fig. S3. Intermolecular NOEs define a previously uncharacterized LM:CXCR4 interface.
  • Fig. S4. CXCR4 residues 7 to 9 form a fourth β strand with LM CXCL12.
  • Fig. S5. Mutation of CXCR4 Ile4 and Ile6 reduces chemokine binding affinity and function.
  • Fig. S6. Energy funnel analysis of the CXCL12:CXCR4 model.
  • Fig. S7. The CXCL12:CXCR4 model demonstrates distinct rotameric states in the TM bundle as a consequence of CXCL12 interactions.
  • Fig. S8. Removal of Lys1 and Pro2 from CXCL12 markedly reduces its receptor binding affinity.
  • Fig. S9. Comparison of the CXCL12:CXCR4 model to all chemokine receptor structures.
  • Fig. S10. Comparison of the CX3CL1:US28 structure to the chemokine-bound CXCR4 structure and model.
  • Fig. S11. Predicted conformational changes involving the TxP2.58xW and CWxP6.50 motifs after the binding of CXCL12 to CXCR4.
  • Fig. S12. Hybrid model–based structural mechanisms for several antagonistic small molecules and inhibitory posttranslational modifications.
  • Table S1. Integrated peak volumes for CXCR4 resonances upon titration of LD and LM.
  • Table S2. NMR refinement statistics for the LM:CXCR41–38 20-model ensemble (PDB 2N55).
  • Table S3. Intermolecular NOEs observed in the LM:CXCR41–38 NMR complex (PDB 2N55).
  • Table S4. Previous mutagenesis studies of residues within and adjacent to the CXCL12:CXCR4 site 1 interface.
  • References (6874)

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Other Supplementary Material for this manuscript includes the following:

  • Data file S1 (.rtf format). Hybrid CXCL12:CXCR4 model from the CXCL12:CXCR4 NMR structure (PDB 2N55) and the CXCR4:IT1t x-ray structure (PDB 3ODU).

Citation: J. J. Ziarek, A. B. Kleist, N. London, B. Raveh, N. Montpas, J. Bonneterre, G. St-Onge, C. J. DiCosmo-Ponticello, C. A. Koplinski, I. Roy, B. Stephens, S. Thelen, C. T. Veldkamp, F. D. Coffman, M. C. Cohen, M. B. Dwinell, M. Thelen, F. C. Peterson, N. Heveker, B. F. Volkman, Structural basis for chemokine recognition by a G protein–coupled receptor and implications for receptor activation. Sci. Signal. 10, eaah5756 (2017).

© 2017 American Association for the Advancement of Science