CCR5 Mutations Distinguish N-Terminal Modifications of RANTES (CCL5) with Agonist versus Antagonist Activity |
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Authors: | Won-Tak Choi Rebecca Nedellec Mia Coetzer Philippe Colin Bernard Lagane Robin E Offord Oliver Hartley Donald E Mosier |
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Institution: | Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA. |
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Abstract: | CCR5 is the major HIV-1 entry coreceptor. RANTES/CCL5 analogs are more potent inhibitors of infection than native chemokines; one class activates and internalizes CCR5, one neither activates nor internalizes, and a third partially internalizes without activation. Here we show that mutations in CCR5 transmembrane domains differentially impact the activity of these three inhibitor classes, suggesting that the transmembrane region of CCR5, a key interaction site for inhibitors, is a sensitive molecular switch, modulating receptor activity. |
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