8SZF: Extracellular calcium-sensing receptor

Cryo-EM structure of cinacalcet-bound active-state human calcium-sensing receptor CaSR in lipid nanodiscs. Determined by electron microscopy at 2.8 Å resolution. Released 7 Feb 2024.

Method: Electron microscopy
Resolution: 2.8 Å
Organism: Homo sapiens
Chains: 2
Atoms: 12,813
Mol. weight: 235.9 kDa
Ligands: SPM, YP4, PO4, CA
Released: 7 Feb 2024

Explore 8SZF in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8SZF contains 68 α-helices and 72 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 32 helices, 35 β-strands

Element	Residues	Length	Sheet
β-strand	26-28	3	1
β-strand	32-38	7	1
β-strand	41	1	2
β-strand	44	1	3
α-helix	55-58	4
β-strand	60	1	3
β-strand	63	1	2
α-helix	65-83	19
β-strand	93-99	7	1
α-helix	104-114	11
α-helix	116-122	7
α-helix	135-137	3
β-strand	138-142	5	1
α-helix	147-157	11
β-strand	164-166	3	1
α-helix	172-175	4
β-strand	183-185	3	1
α-helix	191-203	13
β-strand	208-214	7	4
α-helix	219-232	14
β-strand	236-243	8	4
α-helix	249-260	12
β-strand	266-270	5	4
α-helix	273-286	14
β-strand	292-295	4	4
α-helix	308-310	3
α-helix	311-314	4
β-strand	318-321	4	4
β-strand	325	1	5
α-helix	330-334	5
β-strand	345	1	1
α-helix	348-356	9
β-strand	359	1	6
β-strand	394	1	6
β-strand	414	1	5
α-helix	416-435	20
α-helix	437-438	2
α-helix	452-454	3
α-helix	457-465	9
β-strand	469-470	2	7
β-strand	476-477	2	7
β-strand	489-496	8	4
β-strand	503-511	9	4
β-strand	521-523	3	4
α-helix	525-527	3
α-helix	537-539	3
α-helix	544-546	3
β-strand	550-551	2	8
β-strand	566-567	2	8
β-strand	573	1	9
β-strand	579	1	8
β-strand	583	1	9
β-strand	589-591	3	10
β-strand	598-600	3	10
α-helix	601	1
β-strand	602-604	3	11
α-helix	611-636	26
α-helix	641-645	5
α-helix	648-666	19
α-helix	674-696	23
α-helix	723-745	23
β-strand	749-753	5	11
β-strand	760-766	7	11
α-helix	770-793	24
α-helix	803-820	18
α-helix	822-825	4
α-helix	832-861	30

Chain B: 36 helices, 37 β-strands

Element	Residues	Length	Sheet
β-strand	26-28	3	12
β-strand	32-38	7	12
β-strand	41	1	13
β-strand	44	1	14
β-strand	60	1	14
β-strand	63	1	13
α-helix	65-83	19
β-strand	93-99	7	12
α-helix	104-114	11
α-helix	118-122	5
α-helix	135-137	3
β-strand	138-142	5	12
α-helix	147-157	11
β-strand	164-166	3	12
α-helix	172-175	4
β-strand	183-185	3	12
α-helix	191-203	13
β-strand	208-214	7	15
α-helix	219-231	13
β-strand	236-243	8	15
α-helix	249-260	12
β-strand	266-270	5	15
α-helix	273-286	14
β-strand	292-295	4	15
α-helix	308-310	3
α-helix	311-314	4
β-strand	318-321	4	15
β-strand	325	1	16
α-helix	330-334	5
β-strand	345	1	12
α-helix	348-356	9
β-strand	359	1	17
β-strand	394	1	17
α-helix	401-403	3
β-strand	414	1	16
α-helix	416-435	20
α-helix	445-447	3
α-helix	448-451	4
α-helix	452-454	3
α-helix	457-465	9
β-strand	468-470	3	18
β-strand	476-478	3	18
β-strand	489-496	8	15
β-strand	503-511	9	15
α-helix	516	1
β-strand	521-523	3	15
α-helix	525-527	3
β-strand	530	1	19
β-strand	534	1	19
α-helix	537-539	3
α-helix	544-546	3
β-strand	550-554	5	20
β-strand	563-567	5	20
β-strand	572-573	2	21
β-strand	579	1	20
α-helix	582	1
β-strand	583-584	2	21
β-strand	589-591	3	22
β-strand	598-600	3	22
β-strand	602-604	3	23
α-helix	611-636	26
α-helix	641-644	4
α-helix	648-665	18
α-helix	674-677	4
α-helix	680-697	18
α-helix	721-724	4
α-helix	727-745	19
β-strand	749-753	5	23
β-strand	760-766	7	23
α-helix	770-793	24
α-helix	803-827	25
α-helix	833-860	28
α-helix	871-875	5

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Extracellular calcium-sensing receptor	A	protein	1101	Homo sapiens	P41180 (AlphaFold model)
Extracellular calcium-sensing receptor	B	protein	959	Homo sapiens	P41180 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8SZF_1 Extracellular calcium-sensing receptor (chains A)
DYKDDDDKAAAYGPDQRAQKKGDIILGGLFPIHFGVAAKDQDLKSRPESVECIRYNFRGF
RWLQAMIFAIEEINSSPALLPNLTLGYRIFDTCNTVSKALEATLSFVAQNKIDSLNLDEF
CNCSEHIPSTIAVVGATGSGVSTAVANLLGLFYIPQVSYASSSRLLSNKNQFKSFLRTIP
NDEHQATAMADIIEYFRWNWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYSD
EEEIQHVVEVIQNSTAKVIVVFSSGPDLEPLIKEIVRRNITGKIWLASEAWASSSLIAMP
QYFHVVGGTIGFALKAGQIPGFREFLKKVHPRKSVHNGFAKEFWEETFNCHLQEGAKGPL
PVDTFLRGHEESGDRFSNSSTAFRPLCTGDENISSVETPYIDYTHLRISYNVYLAVYSIA
HALQDIYTCLPGRGLFTNGSCADIKKVEAWQVLKHLRHLNFTNNMGEQVTFDECGDLVGN
YSIINWHLSPEDGSIVFKEVGYYNVYAKKGERLFINEEKILWSGFSREVPFSNCSRDCLA
GTRKGIIEGEPTCCFECVECPDGEYSDETDASACNKCPDDFWSNENHTSCIAKEIEFLSW
TEPFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLLCCFSSSLFF
IGEPQDWTCRLRQPAFGISFVLCISCILVKTNRVLLVFEAKIPTSFHRKWWGLNLQFLLV
FLCTFMQIVICVIWLYTAPPSSYRNQELEDEIIFITCHEGSLMALGFLIGYTCLLAAICF
FFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTYGKFVSAVEVIAILAASFGL
LACIFFNKIYIILFKPSRNTIEEVRCSTAAHAFKVAARATLRRSNVTSTSVTSVNQASTS
RLEGLQSENHRLRMKITELDKDLEEVTMQLQDTPEKKTNSGGSVFTLEDFVGDWEQTAAY
NLDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEV
FKVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNK
IIDERLITPDGSMLFRVTINS

Sequence of entity 2 (B), FASTA

>8SZF_2 Extracellular calcium-sensing receptor (chains B)
WSHPQFEKGGGSGGGSGGSAWSHPQFEKGSAAAYGPDQRAQKKGDIILGGLFPIHFGVAA
KDQDLKSRPESVECIRYNFRGFRWLQAMIFAIEEINSSPALLPNLTLGYRIFDTCNTVSK
ALEATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGVSTAVANLLGLFYIPQVS
YASSSRLLSNKNQFKSFLRTIPNDEHQATAMADIIEYFRWNWVGTIAADDDYGRPGIEKF
REEAEERDICIDFSELISQYSDEEEIQHVVEVIQNSTAKVIVVFSSGPDLEPLIKEIVRR
NITGKIWLASEAWASSSLIAMPQYFHVVGGTIGFALKAGQIPGFREFLKKVHPRKSVHNG
FAKEFWEETFNCHLQEGAKGPLPVDTFLRGHEESGDRFSNSSTAFRPLCTGDENISSVET
PYIDYTHLRISYNVYLAVYSIAHALQDIYTCLPGRGLFTNGSCADIKKVEAWQVLKHLRH
LNFTNNMGEQVTFDECGDLVGNYSIINWHLSPEDGSIVFKEVGYYNVYAKKGERLFINEE
KILWSGFSREVPFSNCSRDCLAGTRKGIIEGEPTCCFECVECPDGEYSDETDASACNKCP
DDFWSNENHTSCIAKEIEFLSWTEPFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKAT
NRELSYLLLFSLLCCFSSSLFFIGEPQDWTCRLRQPAFGISFVLCISCILVKTNRVLLVF
EAKIPTSFHRKWWGLNLQFLLVFLCTFMQIVICVIWLYTAPPSSYRNQELEDEIIFITCH
EGSLMALGFLIGYTCLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYA
STYGKFVSAVEVIAILAASFGLLACIFFNKIYIILFKPSRNTIEEVRCSTAAHAFKVAAR
ATLRRSNVTGSSTNNNEEEKSRLLEKENRELEKIIAEKEERVSELRHQLQSRQQLKKTN

Ligands and cofactors

ID	Name	Formula	Copies
SPM	Spermine	C10 H26 N4	1
YP4	N-[(1R)-1-(naphthalen-1-yl)ethyl]-3-[3-(trifluoromethyl)phenyl]propan-1-amine	C22 H22 F3 N	2
PO4	Phosphate ion	O4 P	2
CA	Calcium ion	Ca	4
TRP	Tryptophan	C11 H12 N2 O2	2
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	5

Primary citation

Allosteric modulation and G-protein selectivity of the Ca 2+ -sensing receptor. He, F., Wu, C.G., Gao, Y. et al. Nature (2024) 626:1141-1148. DOI 10.1038/s41586-024-07055-2 · PubMed

Other PDB entries of the same protein (UniProt P41180 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5FBK 2.1 Å, Crystal structure of the extracellular domain of human calcium sensing receptor
7M3G 2.5 Å, Asymmetric Activation of the Calcium Sensing Receptor Homodimer
5K5S 2.6 Å, Crystal structure of the active form of human calcium-sensing receptor extracellular…
5FBH 2.7 Å, Crystal structure of the extracellular domain of human calcium sensing receptor with…
7SIL 2.7 Å, Structure of positive allosteric modulator-bound active human calcium-sensing receptor
7SIM 2.7 Å, Structure of positive allosteric modulator-free active human calcium-sensing receptor
8WPG 2.7 Å, Human calcium-sensing receptor bound with cinacalcet in detergent
7M3F 2.8 Å, Asymmetric Activation of the Calcium Sensing Receptor Homodimer
9C1P 2.8 Å, Structure of Calcium-Sensing Receptor in complex with positive allosteric modulator '6218
9C2F 2.8 Å, Structure of Calcium-Sensing Receptor in complex with positive allosteric modulator '54149
7E6T 3.0 Å, Structural insights into the activation of human calcium-sensing receptor
5K5T 3.1 Å, Crystal structure of the inactive form of human calcium-sensing receptor extracellular…

Browse structure collections

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