Cryo-EM structure of mouse TPC1 channel in the PtdIns(3,5)P2-bound state

(2R)-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,4,6-trihydroxy-3,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dioctanoate

Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.

Voltage-dependent calcium channel protein TPC1

MAVSLDDDVPLILTLDEAESAPLPPSNSLGQEQLPSKNGGSHSIHNSQVPSLVSGADSPPSSPTGHNWEMNYQEAAIYLQ
EGQNNDKFFTHPKDARALAAYLFVHNHFFYMMELLTALLLLLLSLCESPAVPVLKLHTYVHATLELFALMVVVFELCMKL
RWLGFHTFVRHKRTMVKTSVLVVQFIEAIVVLVRQTSHVRVTRALRCIFLVDCRYCGGVRRNLRQIFQSLPPFMDILLLL
LFFMIIFAILGFYLFSTNPSDPYFSTLENSIVNLFVLLTTANFPDVMMPSYSRNPWSCVFFIVYLSIELYFIMNLLLAVV
FDTFNDIEKHKFKSLLLHKRTAIQHAYGLLASQRRPAGISYRQFEGLMRFYKPRMSARERFLTFKALNQSNTPLLSLKDF
YDIYEVAALQWKAKRNRQHWFDELPRTAFLIFKGINILVNSKAFQYFMYLVVAVNGVWILVETFMLKGGNFTSKHVPWSY
LVFLTIYGVELFMKVAGLGPVEYLSSGWNLFDFSVTAFAFLGLLALTLNMEPFYFIVVLRPLQLLRLFKLKKRYRNVLDT
MFELLPRMASLGLTLLTFYYSFAIVGMEFFNGRLTPNCCNTSTVADAYRFINHTVGNKTKVEEGYYYLNNFDNILNSFVT
LFELTVVNNWYIIMEGVTSQTSHWSRLYFMTFYIVTMVVMTIIVAFILEAFVFRMNYSRKSQDSEVDSGIVIEKEMSKEE
LMAVLELYREERGTSSDVTRLLDTLSQMEKYQQNSMVFLGRRSRTKSDLSLKMYQEEIQEWYEEHAREQEQQKLRGSVPG
PAAQQPPGSRQRSQTVTVEAGLVPR

National Institutes of Health/National Center for Research Resources (NIH/NCRR)

Cancer Prevention and Research Institute of Texas (CPRIT)

Virginia Murchison Linthicum Scholar in Medical Research fund

MAVSLDDDVPLILTLDEAESAPLPPSNSLGQEQLPSKNGGSHSIHNSQVPSLVSGADSPPSSPTGHNWEMNYQEAAIYLQ
EGQNNDKFFTHPKDARALAAYLFVHNHFFYMMELLTALLLLLLSLCESPAVPVLKLHTYVHATLELFALMVVVFELCMKL
RWLGFHTFVRHKRTMVKTSVLVVQFIEAIVVLVRQTSHVRVTRALRCIFLVDCRYCGGVRRNLRQIFQSLPPFMDILLLL
LFFMIIFAILGFYLFSTNPSDPYFSTLENSIVNLFVLLTTANFPDVMMPSYSRNPWSCVFFIVYLSIELYFIMNLLLAVV
FDTFNDIEKHKFKSLLLHKRTAIQHAYGLLASQRRPAGISYRQFEGLMRFYKPRMSARERFLTFKALNQSNTPLLSLKDF
YDIYEVAALQWKAKRNRQHWFDELPRTAFLIFKGINILVNSKAFQYFMYLVVAVNGVWILVETFMLKGGNFTSKHVPWSY
LVFLTIYGVELFMKVAGLGPVEYLSSGWNLFDFSVTAFAFLGLLALTLNMEPFYFIVVLRPLQLLRLFKLKKRYRNVLDT
MFELLPRMASLGLTLLTFYYSFAIVGMEFFNGRLTPNCCNTSTVADAYRFINHTVGNKTKVEEGYYYLNNFDNILNSFVT
LFELTVVNNWYIIMEGVTSQTSHWSRLYFMTFYIVTMVVMTIIVAFILEAFVFRMNYSRKSQDSEVDSGIVIEKEMSKEE
LMAVLELYREERGTSSDVTRLLDTLSQMEKYQQNSMVFLGRRSRTKSDLSLKMYQEEIQEWYEEHAREQEQQKLRGSVPG
PAAQQPPGSRQRSQTVT