Cryo-EM Structure of Ca2+-bound mTMEM16F F518A_Q623A mutant in GDN

Structural basis for the activation of the lipid scramblase TMEM16F.

The map was masked for calculation the final resolution (cryoSPARC auto-masking)

20mM HEPES
150mM NaCl
2mM EGTA
0.03% GDN

Homodimeric mTMEM16F F518A Q623A mutant bound to Ca2+

2mM free Ca2+ added shortly before freezing

Small-conductance calcium-activated nonselective cation channel,SCAN channel,Transmembrane protein 16F

MQMMTRKVLLNMELEEDDDEDGDIVLENFDQTIVCPTFGSLENQQDFRTPEFEEFNGKPDSLFFTDGQRRIDFILVYEDE
SKKENNKKGTNEKQKRKRQAYESNLICHGLQLEATRSVSDDKLVFVKVHAPWEVLCTYAEIMHIKLPLKPNDLKTRSPFG
NLNWFTKVLRVNESVIKPEQEFFTAPFEKSRMNDFYILDRDSFFNPATRSRIVYFILSRVKYQVMNNVNKFGINRLVSSG
IYKAAFPLHDCRFNYESEDISCPSERYLLYREWAHPRSIYKKQPLDLIRKYYGEKIGIYFAWLGYYTQMLLLAAVVGVAC
FLYGYLDQDNCTWSKEVCDPDIGGQILMCPQCDRLCPFWRLNITCESSKKLCIFDSFGTLIFAVFMGVWVTLFLEFWKRR
QAELEYEWDTVELQQEEQARPEYEAQCNHVVINEITQEEERIPFTTCGKCIRVTLCASAVFFWILLIIASVIGIIVYRLS
VFIVFSTTLPKNPNGTDPIQKYLTPQMATSITASIISAIIIMILNTIYEKVAIMITNFELPRTQTDYENSLTMKMFLFQF
VNYYSSCFYIAFFKGKFVGYPGDPVYLLGKYRSEECDPGGCLLELTTQLTIIMGGKAIWNNIAEVLLPWVMNLIGRYKRV
SGSEKITPRWEQDYHLQPMGKLGLFYEYLEMIIQFGFVTLFVASFPLAPLLALVNNILEIRVDAWKLTTQFRRMVPEKAQ
DIGAWQPIMQGIAILAVVTNAMIIAFTSDMIPRLVYYWSFSIPPYGDHTYYTMDGYINNTLSVFNITDFKNTDKENPYIG
LGNYTLCRYRDFRNPPGHPQEYKHNIYYWHVIAAKLAFIIVMEHIIYSVKFFISYAIPDVSKITKSKIKREKYLTQKLLH
ESHLKDLTKNMGIIAERIGGTVDNSVRPKLEALEVLFQGPQGTEQKLISEEDLRGASMDEKTTGWRGGHVVEGLAGELEQ
LRARLEHHPQGQREP

Lipid Scramblase, Ion Channel, Membrane Protein, Blood Coagulation, Viral Entry, Cell Fusion

MQMMTRKVLLNMELEEDDDEDGDIVLENFDQTIVCPTFGSLENQQDFRTPEFEEFNGKPDSLFFTDGQRRIDFILVYEDE
SKKENNKKGTNEKQKRKRQAYESNLICHGLQLEATRSVSDDKLVFVKVHAPWEVLCTYAEIMHIKLPLKPNDLKTRSPFG
NLNWFTKVLRVNESVIKPEQEFFTAPFEKSRMNDFYILDRDSFFNPATRSRIVYFILSRVKYQVMNNVNKFGINRLVSSG
IYKAAFPLHDCRFNYESEDISCPSERYLLYREWAHPRSIYKKQPLDLIRKYYGEKIGIYFAWLGYYTQMLLLAAVVGVAC
FLYGYLDQDNCTWSKEVCDPDIGGQILMCPQCDRLCPFWRLNITCESSKKLCIFDSFGTLIFAVFMGVWVTLFLEFWKRR
QAELEYEWDTVELQQEEQARPEYEAQCNHVVINEITQEEERIPFTTCGKCIRVTLCASAVFFWILLIIASVIGIIVYRLS
VFIVFSTTLPKNPNGTDPIQKYLTPQMATSITASIISFIIIMILNTIYEKVAIMITNFELPRTQTDYENSLTMKMFLFQF
VNYYSSCFYIAFFKGKFVGYPGDPVYLLGKYRSEECDPGGCLLELTTQLTIIMGGKAIWNNIQEVLLPWVMNLIGRYKRV
SGSEKITPRWEQDYHLQPMGKLGLFYEYLEMIIQFGFVTLFVASFPLAPLLALVNNILEIRVDAWKLTTQFRRMVPEKAQ
DIGAWQPIMQGIAILAVVTNAMIIAFTSDMIPRLVYYWSFSIPPYGDHTYYTMDGYINNTLSVFNITDFKNTDKENPYIG
LGNYTLCRYRDFRNPPGHPQEYKHNIYYWHVIAAKLAFIIVMEHIIYSVKFFISYAIPDVSKITKSKIKREKYLTQKLLH
ESHLKDLTKNMGIIAERIGGTVDNSVRPKLE