Sleep research article
Identification of PfSR1-MT as melatonin-responsive GPCR-like candidate from the human malaria parasite <i>Plasmodium falciparum</i>.
Authors: Singh MK , Dias BKM , Ahmed W , Dos Santos Oliveira J , Cecon E , Gbahou F , Torres TM , Guimarães E , Houzé L , Mohanty A , Nakabashi M , Vélez JAC , Giostri VEMA , Paixão MW , Masri B , Jockers R , Garcia CRS
One-line summary
A sleep science research article on Identification of PfSR1-MT as melatonin-responsive GPCR-like candidate from the human malaria parasite <i>Plasmodium falciparum</i>..
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中文解读
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Original abstract
The synchronizing effect of melatonin on the malaria parasite <i>Plasmodium falciparum</i> is well documented, yet its receptor remains elusive. In mammals, melatonin signals through seven-transmembrane (7TM) G protein-coupled receptors. Here, we characterized two putative <i>Plasmodium</i> melatonin receptor candidates, PfSR1-MT and PfSR10, expressed during the asexual parasite stage. We show that PfSR1-MT, but not PfSR10, binds 2-[¹²⁵I]iodomelatonin with high affinity (pM) when heterologously expressed in human cells. Molecular modeling and mutagenesis studies identified the melatonin-binding site within the transmembrane core of PfSR1-MT. Melatonin binding promoted the extracellular domain (ECD) movement of PfSR1-MT and cytosolic Ca²⁺ mobilization. We identified ARL34, an indole compound specifically binding and activating PfSR1-MT, but not human melatonin receptors, and impairing both asexual parasite proliferation and gametocyte development, supporting its potential as a novel antimalarial targeting the PfSR1-MT signaling pathway. Together, these findings identify PfSR1-MT as a melatonin-responsive GPCR-like candidate in the human malaria parasite <i>Plasmodium falciparum</i>.
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