핵심기술
특허 / 논문
| The seventh transmembrane domain of cc chemokine receptor 5 is critical for MIP-1beta binding and receptor activation: role of MET 287. |
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| 등록일 :2022-11-01 16:07 조회수 :204 |
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The seventh transmembrane domain of cc chemokine receptor 5 is critical for MIP-1beta binding and receptor activation: role of MET 287.
Youn B-S, Yu K-Y, Hui Y, Alkhatib G, Kwon BS
Abstract CC chemokine receptor 5 (CCR5) is a high-affinity receptor for macrophage inflammatory protein (MIP)-1beta and functions as the major coreceptor for entry of macrophage-tropic (M-tropic) human immunodeficiency virus type 1 (HIV-1). To evaluate the role of transmembrane domains (TM) in the receptor function of CCR5, the seventh transmembrane domain (TM7) was examined in a series of chimeric receptor constructs including CCR5TM (CCR5 backbone/CCR5 TM7 replaced with CCR1 TM7) and mutants of CCR5TM. The CCR5TM chimera exhibited a dramatic reduction in receptor activation, as well as little or no MIP-1beta binding. Further mutational analysis revealed that Met 287 in TM7 of CCR5 is a critical molecular determinant for both MIP-1beta binding and receptor activation. Interestingly, all of the chimeric/mutated receptors were biologically active in an HIV-1 coreceptor fusion assay, demonstrating that chemokine binding is independent of HIV-1 coreceptor activity. |