Thawj Chaw Tsim Tshuaj High Purity MT2

MT1 thiab MT2 ob leeg koom nrog G protein-coupled receptor (GPCR) superfamily. Lawv cov qauv transmembrane muaj xya -helices, tsim ib qho "serpentine" topology. Thaum melatonin khi rau qhov chaw orthoform ntawm nws cov receptor, nws ua rau muaj kev hloov pauv, ua kom muaj cov protein sib txawv ntawm cov isoforms: MT1 feem ntau yog khub niam txiv rau Gi/o protein, inhibiting adenylate cyclase (AC) kev ua, txo intracellular cAMP qib, thiab yog li inhibiting phosphorylation cascade ntawm cov protein (KAP). MT2, ntawm qhov tod tes, khub niam txiv rau Gi/o thiab Gq proteins, inhibiting cAMP thiab activating phospholipase C (PLC), txhawb IP3 thiab DAG ntau lawm, thiab inducing calcium ion influx. Qhov no "dual-kev taw qhia" ua rau MT1 thiab MT2 ua haujlwm ua ke ntxiv -MT1 dominates "inhibitory signaling," thaum MT2 muaj ob qho tib si "inhibition + excitation" regulatory peev xwm.

Txawm hais tias MT1 thiab MT2 sib koom txog 60% amino acid sequence homology, qhov sib txawv tseem ceeb hauv lawv cov cheeb tsam transmembrane txiav txim siab lawv cov haujlwm tshwj xeeb. MT1 qhov thib peb intracellular voj (ICL3) yog nplua nuj nyob rau hauv cov amino acids yooj yim, ua kom yooj yim khi rau Gi/o proteins; thaum MT2's ICL3 muaj cov cysteine ​​residues tshwj xeeb, uas tuaj yeem tsim cov nyiaj disulfide kom ruaj khov Gq protein sib cuam tshuam. Tsis tas li ntawd, MT2's C-terminus muaj ib pawg ntawm cov chaw phosphorylation, uas tuaj yeem phosphorylated los ntawm G protein-coupled receptor kinase (GRK), yog li nrhiav -arrestin protein thiab mediating receptor endocytosis thiab teeb liab txiav. Cov qauv "molecular fingerprints" no ua rau muaj qhov sib txawv tseem ceeb ntawm MT1 thiab MT2 hauv lub sijhawm teeb tsa thiab kev siv zog.

MT2 lub luag haujlwm tseem ceeb nyob hauv "theem hloov," uas yog, kho lub circadian atherosclerosis theem. Thaum tsaus ntuj, melatonin ua rau MT2 receptors, inhibiting firing kev ua ntawm SCN neurons thiab ncua "lub sij hawm pib" ntawm lub moos lom, cia lub cev hloov mus rau ib tug lig - mus rau - pw, lig - rau - tsaug zog; thaum ua ntej kaj ntug, MT2 ua kom nce qib, pab lub cev hloov mus rau thaum ntxov - mus rau - pw, ntxov- rau - sawv qauv. Qhov no "theem hloov" mechanism tso siab rau MT2 qhov inhibition ntawm cAMP thiab kev tswj ntawm calcium ions: txo cAMP qib txo CREB protein phosphorylation, yog li inhibiting transcription ntawm Per1 / Per2 noob; thaum calcium ion influx activates calmodulin kinase (CaMK), txhawb nqa Cry noob qhia, thaum kawg ua tiav "lub sij hawm rov pib dua" ntawm lub moos lom.

Los ntawm qhov kev xav ntawm evolutionary, qhov kev ua haujlwm sib txawv ntawm MT1 thiab MT2 yog tsav los ntawm kev xaiv zoo. Cov noob MT1 tau txais kev txuag thoob plaws ntau hom, feem ntau yog ua kom huv si, khaws nws cov lus teb rau melatonin; thaum lub MT2 noob nthuav tawm cov yam ntxwv tseem ceeb ntawm kev xaiv, nrog ntau dua amino acid hloov zaus nyob rau hauv nws cheeb tsam transmembrane thiab intracellular voj, qhia txog lub luag hauj lwm hloov tau yooj yim dua rau kev hloov pauv hauv ib puag ncig photoperiod. Qhov "conservatism + innovation" evolutionary lub tswv yim tso cai rau MT1 thiab MT2 tswj lawv cov basal rhythms thaum tiv nrog lub teeb thiab tsaus variations ntawm txawv latitudes, muab molecular - theem adaptive zoo rau cov ciaj sia taus thiab reproduction ntawm cov kab mob.

Hauv cov ntsiab lus, MT1 thiab MT2 ua zoo li "dual engines" nyob rau hauv lub circadian atherosclerosis system. Los ntawm G protein-coupled "dual-cov cim taw qhia," cov qauv sib txawv tsim "molecular fingerprints," theem hloov muab "lub sij hawm calibration," thiab evolutionary "zoo xaiv," lawv sib sau ua ke tsim lub neej mechanism rau kev nkag siab thiab teb rau lub sijhawm. Lawv tsis yog lub hom phiaj tseem ceeb rau kev tswj hwm kev pw tsaug zog nkaus xwb tab sis kuj yog "cov txuas txuas molecular" txuas ib puag ncig cov cim thiab cov cellular metabolism, muab cov tswv yim tshiab rau kev kho mob insomnia, kev nyuaj siab, thiab metabolic syndrome.