9AXF: Human calcium-sensing receptor

Structure of human calcium-sensing receptor in complex with chimeric Gq (miniGisq) protein in detergent. Determined by electron microscopy at 3.5 Å resolution. Released 17 Apr 2024.

Method: Electron microscopy
Resolution: 3.5 Å
Organisms: Homo sapiens, Mus musculus, Lama glama
Chains: 7
Atoms: 21,342
Mol. weight: 340.56 kDa
Ligands: NAG, TCR, PO4, CLR
Released: 17 Apr 2024

Explore 9AXF in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9AXF contains 98 α-helices and 141 β-strands across 7 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: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	7-32	26
β-strand	34-39	6	25
β-strand	71-75	5	25
β-strand	80-84	5	25
α-helix	96-99	4
β-strand	105-111	7	25
α-helix	118-129	12
α-helix	132-134	3
β-strand	138-144	7	25
α-helix	146-155	10
α-helix	160-163	4
α-helix	165-167	3
α-helix	184-201	18
β-strand	211-215	5	25
α-helix	223-242	20

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-23	20
α-helix	30-33	4
β-strand	47-51	5	26
β-strand	58-63	6	27
β-strand	69-74	6	27
β-strand	78-83	6	27
β-strand	88-94	7	27
β-strand	100-105	6	28
β-strand	111-116	6	28
β-strand	120-125	6	28
β-strand	134-140	7	28
β-strand	146-153	8	29
β-strand	156-161	6	29
β-strand	165-170	6	29
β-strand	175-181	7	29
β-strand	187-192	6	30
β-strand	198-203	6	30
β-strand	207-212	6	30
β-strand	217-223	7	30
β-strand	229-234	6	31
β-strand	240-245	6	31
β-strand	250-254	5	31
β-strand	259-264	6	31
β-strand	273-278	6	32
β-strand	284-289	6	32
β-strand	294-298	5	32
β-strand	303-308	6	32
β-strand	315-320	6	26
β-strand	327-331	5	26
β-strand	336-339	4	26

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	9-23	15
α-helix	26-27	2
α-helix	30-43	14
α-helix	53-55	3

Chain H: 6 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	23-27	5	33
β-strand	30-32	3	34
β-strand	38-45	8	33
α-helix	49-51	3
β-strand	53-59	7	34
β-strand	65-71	7	34
β-strand	78-80	3	34
α-helix	82-84	3
β-strand	88-93	6	33
α-helix	94-96	3
β-strand	98-103	6	33
α-helix	108-110	3
β-strand	112-119	8	34
β-strand	130-131	2	34
β-strand	136-139	4	34
β-strand	160-162	3	35
β-strand	166	1	36
β-strand	175-181	7	35
β-strand	186	1	37
β-strand	192	1	37
β-strand	194-199	6	36
β-strand	206-210	5	36
β-strand	214-215	2	36
β-strand	223-228	6	35
β-strand	231-236	6	35
α-helix	241-243	3
β-strand	246-251	6	36
α-helix	257	1
β-strand	258-259	2	36
β-strand	263-264	2	36

Chain N: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	38
β-strand	11	1	39
β-strand	17-25	9	38
α-helix	29-31	3
β-strand	34-39	6	40
β-strand	45-51	7	40
β-strand	58-60	3	40
β-strand	68-73	6	38
β-strand	78-84	7	38
α-helix	88-90	3
β-strand	92-98	7	40
β-strand	122-124	3	40
β-strand	125	1	39

Chain Q: 36 helices, 35 β-strands

Element	Residues	Length	Sheet
α-helix	22-24	3
β-strand	26-28	3	14
β-strand	32-38	7	14
β-strand	44	1	15
β-strand	60	1	15
α-helix	65-83	19
β-strand	93-99	7	14
α-helix	104-114	11
α-helix	116-120	5
β-strand	129-130	2	4
β-strand	138-142	5	14
α-helix	147-158	12
β-strand	164-166	3	14
α-helix	172-175	4
β-strand	183-185	3	14
α-helix	191-203	13
β-strand	208-214	7	16
α-helix	219-232	14
β-strand	236-243	8	16
α-helix	249-261	13
β-strand	266-270	5	16
α-helix	273-286	14
β-strand	292-295	4	16
α-helix	296	1
α-helix	308-310	3
α-helix	311-314	4
β-strand	318-322	5	16
α-helix	323-324	2
β-strand	325	1	17
α-helix	330-335	6
β-strand	345	1	14
α-helix	348-356	9
β-strand	359	1	18
α-helix	393	1
β-strand	394	1	18
α-helix	395	1
α-helix	401-403	3
β-strand	414	1	17
α-helix	416-435	20
α-helix	445-447	3
α-helix	457-465	9
β-strand	469-470	2	19
β-strand	476-477	2	19
β-strand	489-496	8	16
β-strand	503-511	9	16
β-strand	521-523	3	16
α-helix	525-527	3
β-strand	530	1	20
β-strand	534	1	20
β-strand	550-554	5	21
α-helix	555	1
β-strand	563-567	5	21
α-helix	568-569	2
β-strand	573	1	22
β-strand	583	1	22
β-strand	589-591	3	23
β-strand	598-600	3	23
α-helix	601	1
β-strand	602-604	3	24
α-helix	611-636	26
α-helix	641-644	4
α-helix	648-664	17
α-helix	665-668	4
α-helix	674-698	25
α-helix	724-745	22
β-strand	749-753	5	24
β-strand	760-766	7	24
α-helix	770-793	24
α-helix	799-827	29
α-helix	833-852	20
α-helix	854-861	8

Chain R: 39 helices, 37 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
β-strand	60	1	3
β-strand	63	1	2
α-helix	65-83	19
β-strand	93-99	7	1
α-helix	104-115	12
α-helix	118-121	4
α-helix	128-129	2
β-strand	130-131	2	4
β-strand	138-142	5	1
α-helix	147-159	13
β-strand	164-166	3	1
α-helix	172-175	4
β-strand	184-185	2	1
α-helix	191-203	13
β-strand	208-214	7	5
α-helix	219-232	14
β-strand	236-243	8	5
α-helix	249-261	13
β-strand	266-270	5	5
α-helix	273-286	14
β-strand	292-295	4	5
α-helix	308-310	3
α-helix	311-314	4
β-strand	318-322	5	5
α-helix	330-335	6
β-strand	345	1	1
α-helix	348-356	9
β-strand	359	1	6
α-helix	393	1
β-strand	394	1	6
α-helix	395	1
α-helix	401-403	3
α-helix	416-435	20
α-helix	445-447	3
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	5
β-strand	503-511	9	5
α-helix	516	1
β-strand	521-523	3	5
β-strand	530	1	8
β-strand	534	1	8
α-helix	537-539	3
β-strand	550-551	2	9
β-strand	554	1	10
α-helix	555	1
β-strand	563	1	10
β-strand	566-567	2	9
α-helix	568-569	2
β-strand	572-573	2	11
β-strand	583-584	2	11
β-strand	589-591	3	12
β-strand	598-600	3	12
α-helix	601	1
β-strand	602-604	3	13
α-helix	611-636	26
α-helix	641-645	5
α-helix	648-668	21
α-helix	674-706	33
α-helix	717-745	29
β-strand	749-753	5	13
β-strand	760-766	7	13
α-helix	770-793	24
α-helix	805-809	5
α-helix	810-817	8
α-helix	818-820	3
α-helix	822-826	5
α-helix	831-861	31
α-helix	864-866	3
α-helix	869-881	13

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Extracellular calcium-sensing receptor	Q, R	protein	911	Homo sapiens	P41180 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-1,Adenylate cyclase-stimulating G alpha…	A	protein	246	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	348	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
Single-chain antibody fragment scFv16	H	protein	297	Mus musculus
Nanobody Nb-35	N	protein	160	Lama glama

Sequence of entity 1 (Q, R), FASTA

>9AXF_1 Extracellular calcium-sensing receptor (chains Q, R)
MAFYSCCWVLLALTWHTSAYGPDQRAQKKGDIILGGLFPIHFGVAAKDQDLKSRPESVEC
IRYNFRGFRWLQAMIFAIEEINSSPALLPNLTLGYRIFDTCNTVSKALEATLSFVAQNKI
DSLNLDEFCNCSEHIPSTIAVVGATGSGVSTAVANLLGLFYIPQVSYASSSRLLSNKNQF
KSFLRTIPNDEHQATAMADIIEYFRWNWVGTIAADDDYGRPGIEKFREEAEERDICIDFS
ELISQYSDEEEIQHVVEVIQNSTAKVIVVFSSGPDLEPLIKEIVRRNITGKIWLASEAWA
SSSLIAMPQYFHVVGGTIGFALKAGQIPGFREFLKKVHPRKSVHNGFAKEFWEETFNCHL
QEGAKGPLPVDTFLRGHEESGDRFSNSSTAFRPLCTGDENISSVETPYIDYTHLRISYNV
YLAVYSIAHALQDIYTCLPGRGLFTNGSCADIKKVEAWQVLKHLRHLNFTNNMGEQVTFD
ECGDLVGNYSIINWHLSPEDGSIVFKEVGYYNVYAKKGERLFINEEKILWSGFSREVPFS
NCSRDCLAGTRKGIIEGEPTCCFECVECPDGEYSDETDASACNKCPDDFWSNENHTSCIA
KEIEFLSWTEPFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLLC
CFSSSLFFIGEPQDWTCRLRQPAFGISFVLCISCILVKTNRVLLVFEAKIPTSFHRKWWG
LNLQFLLVFLCTFMQIVICVIWLYTAPPSSYRNQELEDEIIFITCHEGSLMALGFLIGYT
CLLAAICFFFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTYGKFVSAVEVIA
ILAASFGLLACIFFNKIYIILFKPSRNTIEEVRCSTAAHAFKVAARATLRRSNVSRKRSS
SLGDYKDDDDK

Sequence of entity 2 (A), FASTA

>9AXF_2 Guanine nucleotide-binding protein G(i) subunit alpha-1,Adenylate cyclase-stimulating G alpha protein (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRILHGGS
GGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQE
ALNDFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEP
GEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENARRIFNDCKDIILQMNL
REYNLV

Sequence of entity 3 (B), FASTA

>9AXF_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MDYKDDDDKSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLR
GHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYV
ACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIE
TGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAI
CFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDF
NCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (G), FASTA

>9AXF_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (H), FASTA

>9AXF_5 Single-chain antibody fragment scFv16 (chains H)
MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSC
SASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQ
MTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQ
ATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDR
FSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLELKAAAHHHHHHHH

Sequence of entity 6 (N), FASTA

>9AXF_6 Nanobody Nb-35 (chains N)
MKYLLPTAAAGLLLLAAQPAMAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVR
QAPGKGLEWVSDISQSGASISYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCAR
CPAPFTRDCFDVTSTTYAYRGQGTQVTVSSHHHHHHEPEA

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	8
TCR	Cyclomethyltryptophan	C12 H12 N2 O2	2
PO4	Phosphate ion	O4 P	2
CLR	Cholesterol	C27 H46 O	8
Y01	Cholesterol hemisuccinate	C31 H50 O4	4
AV0	Lauryl Maltose Neopentyl Glycol	C47 H88 O22	1
9IG	3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]propan-1-amine	C18 H22 Cl N O	2
CA	Calcium ion	Ca	7

Primary citation

Promiscuous G-protein activation by the calcium-sensing receptor. Zuo, H., Park, J., Frangaj, A. et al. Nature (2024) 629:481-488. DOI 10.1038/s41586-024-07331-1 · 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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