Research ArticleBiochemistry

Structure-function guided modeling of chemokine-GPCR specificity for the chemokine XCL1 and its receptor XCR1

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Science Signaling  03 Sep 2019:
Vol. 12, Issue 597, eaat4128
DOI: 10.1126/scisignal.aat4128

Modeling ligand-receptor specificity

Ligand-receptor interactions trigger many cellular behaviors and changes that underlie various physiologic processes. Understanding what determines the specificity of these interactions, therefore, can explain disease and inform the development of targeted therapeutics. Using a hybrid modeling approach, Fox et al. generated a model for the chemokine XCL1 in complex with its G protein–coupled receptor XCR1 and identified key interaction sites. Changes within a region of XCL1 that determined its binding energy to XCR1 changed the activity of the receptor and, consequently, cell migration. In addition to showing the power of such hybrid approaches, these findings specifically on this chemokine signaling axis may have implications for diseases associated with altered dendritic and T cell immune responses.

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