8WPU: Human calcium-sensing receptor(CaSR)

Human calcium-sensing receptor(CaSR) bound to cinacalcet in complex with Gq protein. Determined by electron microscopy at 3.1 Å resolution. Released 22 Nov 2023.

Method: Electron microscopy
Resolution: 3.1 Å
Organisms: Homo sapiens, Rattus norvegicus
Chains: 6
Atoms: 18,794
Mol. weight: 354.72 kDa
Ligands: YP4, PO4, TRP, NAG
Released: 22 Nov 2023

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

Secondary structure: helices and β-sheets

8WPU contains 103 α-helices and 135 β-strands across 6 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: 44 helices, 35 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	116-123	8
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	190-203	14
β-strand	208-214	7	15
α-helix	219-232	14
β-strand	236-243	8	15
α-helix	249-261	13
β-strand	266-270	5	15
α-helix	273-285	13
β-strand	292-295	4	15
α-helix	308-310	3
α-helix	311-314	4
β-strand	318-322	5	15
α-helix	323-324	2
β-strand	325	1	16
α-helix	330-335	6
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	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
α-helix	530-532	3
α-helix	537-539	3
α-helix	544-546	3
β-strand	550-554	5	19
α-helix	555	1
β-strand	563-567	5	19
β-strand	572-573	2	20
α-helix	582	1
β-strand	583-584	2	20
α-helix	585-586	2
β-strand	589-591	3	21
β-strand	598-600	3	21
α-helix	601	1
β-strand	602	1	22
α-helix	603	1
α-helix	611-636	26
α-helix	641-645	5
α-helix	648-663	16
α-helix	664-667	4
α-helix	675-678	4
α-helix	681-705	25
α-helix	723-743	21
β-strand	749-753	5	23
β-strand	760	1	22
β-strand	762-766	5	23
α-helix	770-793	24
α-helix	799-801	3
α-helix	804-820	17
α-helix	822-827	6
α-helix	832-849	18
α-helix	850-854	5
α-helix	855-861	7

Chain B: 36 helices, 32 β-strands

Element	Residues	Length	Sheet
β-strand	26-28	3	1
β-strand	32-38	7	1
β-strand	44	1	2
α-helix	53-55	3
α-helix	57-59	3
β-strand	60	1	2
α-helix	65-83	19
β-strand	93-99	7	1
α-helix	104-114	11
α-helix	116-123	8
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	192-203	12
β-strand	208-214	7	3
α-helix	219-232	14
β-strand	236-243	8	3
α-helix	249-260	12
β-strand	266-270	5	3
α-helix	273-286	14
β-strand	292-295	4	3
α-helix	308-310	3
β-strand	318	1	3
β-strand	319-322	4	4
α-helix	323-324	2
β-strand	325	1	5
α-helix	330-335	6
α-helix	348-356	9
α-helix	401-403	3
β-strand	414	1	5
α-helix	416-435	20
α-helix	452-454	3
α-helix	457-465	9
β-strand	469-470	2	6
β-strand	476-477	2	6
β-strand	489-496	8	4
β-strand	503-511	9	4
α-helix	516	1
β-strand	521-523	3	4
α-helix	525-527	3
α-helix	537-539	3
α-helix	544-546	3
β-strand	550-554	5	7
β-strand	563-567	5	7
α-helix	568-569	2
β-strand	572-573	2	8
α-helix	582	1
β-strand	583-584	2	8
α-helix	585	1
β-strand	590-591	2	9
β-strand	598-599	2	9
β-strand	602-604	3	10
α-helix	613-636	24
α-helix	643-646	4
α-helix	648-664	17
α-helix	665-667	3
α-helix	674-698	25
α-helix	724-745	22
β-strand	749	1	11
β-strand	752-753	2	10
β-strand	760-763	4	10
β-strand	766	1	11
α-helix	770-792	23
α-helix	803-825	23
α-helix	837-860	24
α-helix	863-867	5

Chain C: 6 helices, 32 β-strands

Element	Residues	Length	Sheet
α-helix	2-5	4
α-helix	13-22	10
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	25
β-strand	58-63	6	26
β-strand	69-74	6	26
β-strand	78-83	6	26
β-strand	88-94	7	26
β-strand	100-105	6	27
β-strand	111-116	6	27
β-strand	121-125	5	27
β-strand	134-139	6	27
α-helix	145	1
β-strand	146-151	6	28
β-strand	157-161	5	28
β-strand	165-169	5	28
β-strand	176-181	6	28
β-strand	187	1	29
β-strand	191-192	2	30
β-strand	198-202	5	30
β-strand	203	1	29
β-strand	208-212	5	30
β-strand	218-222	5	30
β-strand	229-234	6	31
β-strand	240-245	6	31
β-strand	249-254	6	31
β-strand	259-262	4	31
α-helix	272	1
β-strand	273-278	6	32
β-strand	284-289	6	32
β-strand	294-298	5	32
β-strand	303-306	4	32
β-strand	315-317	3	25
β-strand	320	1	25
β-strand	327	1	25
β-strand	330-331	2	25
β-strand	336-339	4	25

Chain D: 5 helices, 0 β-strands

Element	Residues	Length
α-helix	12	1
α-helix	13-17	5
α-helix	19-22	4
α-helix	31-43	13
α-helix	53-55	3

Chain E: 4 helices, 30 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	33
β-strand	10	1	34
β-strand	18-25	8	33
α-helix	29-31	3
β-strand	33-34	2	35
β-strand	35-39	5	36
β-strand	45-50	6	36
β-strand	51	1	37
β-strand	58	1	37
α-helix	62-64	3
β-strand	68-69	2	33
β-strand	72-73	2	33
β-strand	78-83	6	33
β-strand	92-94	3	34
β-strand	95	1	36
β-strand	97-99	3	35
β-strand	110-111	2	35
α-helix	112	1
β-strand	113	1	33
α-helix	114	1
β-strand	115-117	3	34
β-strand	129	1	38
β-strand	134-136	3	39
β-strand	142-148	7	38
β-strand	154	1	40
β-strand	160	1	40
β-strand	163-166	4	41
β-strand	174-178	5	41
β-strand	182	1	41
β-strand	195-196	2	38
β-strand	199-205	7	38
β-strand	216-218	3	41
β-strand	227	1	41
β-strand	232-234	3	39

Chain G: 8 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-32	26
β-strand	34-40	7	24
α-helix	42-44	3
α-helix	46-49	4
β-strand	70-76	7	24
β-strand	79-85	7	24
β-strand	105-111	7	24
α-helix	118-129	12
β-strand	138-144	7	24
α-helix	147-153	7
α-helix	160-162	3
α-helix	184-201	18
β-strand	212-213	2	24
α-helix	223-242	20

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Extracellular calcium-sensing receptor,calcium-sensing receptor	A, B	protein	1076	Homo sapiens	P41180 (AlphaFold model)
G subunit q (Gi2-mini-Gq chimeric)	G	protein	246	Homo sapiens	P04899 (AlphaFold model), P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	C	protein	376	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	D	protein	71	Homo sapiens	P59768
ScFv16	E	protein	297	Rattus norvegicus

Sequence of entity 1 (A, B), FASTA

>8WPU_1 Extracellular calcium-sensing receptor,calcium-sensing receptor (chains A, B)
MKTIIALSYIFCLVFADYKDDDDENLYFQGYGPDQRAQKKGDIILGGLFPIHFGVAAKDQ
DLKSRPESVECIRYNFRGFRWLQAMIFAIEEINSSPALLPNLTLGYRIFDTCNTVSKALE
ATLSFVAQNKIDSLNLDEFCNCSEHIPSTIAVVGATGSGVSTAVANLLGLFYIPQVSYAS
SSRLLSNKNQFKSFLRTIPNDEHQATAMADIIEYFRWNWVGTIAADDDYGRPGIEKFREE
AEERDICIDFSELISQYSDEEEIQHVVEVIQNSTAKVIVVFSSGPDLEPLIKEIVRRNIT
GKIWLASEAWASSSLIAMPQYFHVVGGTIGFALKAGQIPGFREFLKKVHPRKSVHNGFAK
EFWEETFNCHLQEGAKGPLPVDTFLRGHEESGDRFSNSSTAFRPLCTGDENISSVETPYI
DYTHLRISYNVYLAVYSIAHALQDIYTCLPGRGLFTNGSCADIKKVEAWQVLKHLRHLNF
TNNMGEQVTFDECGDLVGNYSIINWHLSPEDGSIVFKEVGYYNVYAKKGERLFINEEKIL
WSGFSREVPFSNCSRDCLAGTRKGIIEGEPTCCFECVECPDGEYSDETDASACNKCPDDF
WSNENHTSCIAKEIEFLSWTEPFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRE
LSYLLLFSLLCCFSSSLFFIGEPQDWTCRLRQPAFGISFVLCISCILVKTNRVLLVFEAK
IPTSFHRKWWGLNLQFLLVFLCTFMQIVICVIWLYTAPPSSYRNQELEDEIIFITCHEGS
LMALGFLIGYTCLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTY
GKFVSAVEVIAILAASFGLLACIFFNKIYIILFKPSRNTIEEVRCSTAAHAFKVAARATL
RRSGSSGGGGSGGGGSSGVFTLEDFVGDWEQTAAYNLDQVLEQGGVSSLLQNLAVSVTPI
QRIVRSGENALKIDIHVIIPYEGLSADQMAQIEEVFKVVYPVDDHHFKVILPYGTLVIDG
VTPNMLNYFGRPYEGIAVFDGKKITVTGTLWNGNKIIDERLITPDGSMLFRVTINS

Sequence of entity 2 (G), FASTA

>8WPU_2 G subunit q (Gi2-mini-Gq chimeric) (chains G)
MGSTVSAEDKAAAERSKMIDKNLREDGEKARRTLRLLLLGADNSGKSTIVKQMRILHGGS
GGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRKEFVDISTASGDGRHICYPHFTCAVDTENARRIFNDCKDIILQMNL
REYNLV

Sequence of entity 3 (C), FASTA

>8WPU_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains C)
HHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRT
LRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGN
YVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWD
IETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDIN
AICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYD
DFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSGG
GGSSGVSGWRLFKKIS

Sequence of entity 4 (D), FASTA

>8WPU_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains D)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (E), FASTA

>8WPU_5 ScFv16 (chains E)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSC
SASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQ
MTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLELKAAAHHHHHHHH

Ligands and cofactors

ID	Name	Formula	Copies
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
TRP	Tryptophan	C11 H12 N2 O2	2
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	9
CLR	Cholesterol	C27 H46 O	1
CA	Calcium ion	Ca	4

Primary citation

Structural insights into asymmetric activation of the calcium-sensing receptor-G q complex. Ling, S., Meng, X., Zhang, Y. et al. Cell Res (2024) 34:169-172. DOI 10.1038/s41422-023-00892-2 · 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
8SZF 2.8 Å, Cryo-EM structure of cinacalcet-bound active-state human calcium-sensing receptor CaSR…
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

Browse structure collections

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