1.A.4.5.14
TrpM5 of 1165 aas and 8 - 10 TMSs. cryo-EM structures have been solved in an apo closed state, a Ca2+-bound open state, and an antagonist-bound inhibited state. Ruan et al. 2021 defined two novel ligand binding sites: a Ca2+ site (CaICD) in the intracellular domain and an antagonist site in the transmembrane domain (TMD). The CaICD site is unique to TRPM5 and has two roles: modulating the voltage dependence and promoting Ca2+ binding to the CaTMD site, which is conserved throughout TRPM channels. Conformational changes initialized from both Ca2+ sites cooperatively open the ion-conducting pore. The antagonist NDNA wedges into the space between the S1-S4 domain and the pore domain, stabilizing the transmembrane domain in an apo-like closed state (Ruan et al. 2021). It and phospholipase C-β2 colocalize in taste receptor cells (Yoshida et al. 2007).
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| Accession Number: | S5UH55 |
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| Protein Name: | Transient receptor potential melastatin 5 |
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| Length: | 1165 |
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| Molecular Weight: | 132641.00 |
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| Species: | Danio rerio (Zebrafish) [7955] |
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| Number of TMSs: | 8 |
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| Location1 / Topology2 / Orientation3: |
Membrane1 / Multi-pass membrane protein2 |
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| Substrate |
sodium(1+), potassium(1+), caesium ion |
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1: MVEKSSERFD KQMAGRLGDI DFTGVSRTRG KFVRVTSSTD PAEIYQILTK QWGLAPPHLV
61: VALMGGDEVA QLKPWLRDTL RKGLVKAAQS TGAWILTSGL RFGITKNLGQ AVRDHSLAST
121: SPKVRVVAIG IAPWNMIQNR DLLLSAKPDH PATYPTEDLP YGAVYSLDCN HSHFILVDED
181: PKRPGATGEM RVKMLKHISL QRTGYGGTGS IEIPVLCLLV HGEPRILQKM YKNIQNSIPW
241: LILAGSGGVA DILVTLMDRG CWDADIVQEL LINTFPDGLH STEITSWTKL IQRILDHGHL
301: LTVHDPEQDS ELDTVILKAL VKACKSQSQE AQDFLDELKL AVAWNRVDIA KSEIFSGDVQ
361: WSAQDLEEVM MEALVNDKPD FVRLFVDNGV NIKQFLTYGR LQELYCSVSE KNLLHTLLLK
421: KNQERQAQLA RKRMSGNPNN ELGDRKFRFT FHEVSKVLKD FLDDTCKGFY QKLPAERMGK
481: GRLFHSQKNL PDMDRRCEHP WRDLFLWAIL QNRQEMANYF WAMGPEAVAA ALVGCKIMKE
541: MAHLATEAES ARSMKNAKYE QFAMDLFSEC YSNSEDRAYS LLVRKTCCWS KATVLNIATL
601: AEAKCFFAHD GVQALLTKVW WGAMRTDTSI SRLVLTFFIP PLVWTSLIKF NPEEQVSKDE
661: GEPFAELDSL ETEQALLLTD GDPVAGEGSA ETAARSCSAT FIRVVLRRWN RFWSAPVTVF
721: MGNVIMYFAF LILFSYVLLL DFRPPPPYGP SAAEIILYFW VFTLVLEEIR QSFFTDEDMS
781: ILKKMKLYVE DNWNKCDMVA ISLFVVGLSC RMAMSTYEAG RTVLALDFMV FTLRLIHIFA
841: IHKQLGPKII IVERMIKDVF FFLFFLSVWL IAYGVTTQAL LHPNDPRIDW VFRRALYRPY
901: LHIFGQIPLE EIDAAKMPDD NCTTDVQEII LGTLPPCPNI YANWLVILLL VIYLLVTNVL
961: LLNLLIAMFS YTFQVVQENA DIFWKFQRYN LIVEYHSRPA LAPPFIIISH ITQALLSFIK
1021: KTENTQDLLE RELPSGLDQK LMTWETVQKE NYLAKLEHEH RESSGERLRY TSSKVQTLLR
1081: MVGGFKDQEK RMATVETEVR YCGEVLSWIA ECFHKSTLKC DRDAPKAPRS IAGSSRDQQP
1141: QGAKRQQPGG HPAYGTDKKL PFIDH