8SZH: Extracellular calcium-sensing receptor

Cryo-EM structure of cinacalcet-bound human calcium-sensing receptor CaSR-Gi complex in lipid nanodiscs. Determined by electron microscopy at 3.1 Å resolution. Released 7 Feb 2024.

Method: Electron microscopy
Resolution: 3.1 Å
Organism: Homo sapiens
Chains: 5
Atoms: 18,062
Mol. weight: 292.06 kDa
Ligands: YP4, PCW, NAG, CA
Released: 7 Feb 2024

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

Secondary structure: helices and β-sheets

8SZH contains 87 α-helices and 110 β-strands across 5 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: 37 helices, 34 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	65-82	18
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	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
α-helix	322-324	3
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
α-helix	392-393	2
β-strand	394	1	6
α-helix	395	1
β-strand	414	1	5
α-helix	416-435	20
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	550-552	3	8
β-strand	565-567	3	8
α-helix	568-569	2
β-strand	572-573	2	9
α-helix	582	1
β-strand	583-584	2	9
α-helix	585-586	2
β-strand	589-591	3	10
β-strand	598-600	3	10
β-strand	602-604	3	11
α-helix	611-636	26
α-helix	641-645	5
α-helix	648-663	16
α-helix	664-668	5
α-helix	676-706	31
α-helix	711-712	2
α-helix	715-718	4
α-helix	723-745	23
β-strand	750-753	4	11
β-strand	760-765	6	11
α-helix	771-792	22
α-helix	804-820	17
α-helix	822-827	6
α-helix	832-861	30
α-helix	869-876	8

Chain B: 33 helices, 36 β-strands

Element	Residues	Length	Sheet
β-strand	26-27	2	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	65-82	18
β-strand	93-99	7	12
α-helix	104-112	9
α-helix	116-123	8
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	219-232	14
β-strand	236-243	8	15
α-helix	249-259	11
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	417-435	19
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
β-strand	521-523	3	15
α-helix	525-527	3
β-strand	530	1	19
β-strand	534	1	19
α-helix	544-546	3
β-strand	550-553	4	20
β-strand	564-567	4	20
β-strand	572-573	2	21
β-strand	583-584	2	21
α-helix	585	1
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	641-645	5
α-helix	648-663	16
α-helix	664-668	5
α-helix	680-698	19
α-helix	700-703	4
α-helix	725-745	21
β-strand	751-753	3	23
β-strand	760-764	5	23
α-helix	770-792	23
α-helix	803-826	24
α-helix	833-849	17
α-helix	850-854	5
α-helix	855-860	6

Chain C: 10 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	8-30	23
β-strand	34-38	5	24
α-helix	48-52	5
β-strand	186-190	5	24
β-strand	195-199	5	24
α-helix	208-210	3
α-helix	212-215	4
β-strand	220-226	7	24
α-helix	227-230	4
β-strand	234	1	25
β-strand	241	1	25
α-helix	242-254	13
β-strand	263-269	7	24
α-helix	271-278	8
α-helix	283-285	3
α-helix	296-308	13
β-strand	319-323	5	24
α-helix	331-351	21

Chain D: 5 helices, 32 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-34	5
β-strand	47-51	5	26
β-strand	58-61	4	27
β-strand	69	1	28
β-strand	72-74	3	27
β-strand	79-81	3	27
β-strand	83	1	28
β-strand	91-92	2	27
β-strand	100	1	29
β-strand	104-105	2	30
β-strand	111-113	3	30
β-strand	116	1	29
β-strand	121-125	5	30
β-strand	135-139	5	30
β-strand	146-151	6	31
β-strand	157-161	5	31
β-strand	165-168	4	31
β-strand	178-181	4	31
β-strand	187-192	6	32
β-strand	198-203	6	32
β-strand	208-212	5	32
β-strand	218-222	5	32
β-strand	229-234	6	33
β-strand	240-245	6	33
β-strand	250-254	5	33
β-strand	259-264	6	33
α-helix	272	1
β-strand	273-278	6	34
α-helix	279	1
α-helix	280-282	3
β-strand	284-289	6	34
β-strand	294-298	5	34
β-strand	306-308	3	34
β-strand	315-320	6	26
β-strand	327-331	5	26
β-strand	336-339	4	26

Chain E: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	9-23	15
α-helix	30-43	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Extracellular calcium-sensing receptor	A, B	protein	886	Homo sapiens	P41180 (AlphaFold model)
Guanine nucleotide-binding protein G(i) subunit alpha-3	C	protein	354	Homo sapiens	P08754 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	D	protein	343	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	E	protein	71	Homo sapiens	P59768 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8SZH_1 Extracellular calcium-sensing receptor (chains A, B)
DYKDDDDKAAAYGPDQRAQKKGDIILGGLFPIHFGVAAKDQDLKSRPESVECIRYNFRGF
RWLQAMIFAIEEINSSPALLPNLTLGYRIFDTCNTVSKALEATLSFVAQNKIDSLNLDEF
CNCSEHIPSTIAVVGATGSGVSTAVANLLGLFYIPQVSYASSSRLLSNKNQFKSFLRTIP
NDEHQATAMADIIEYFRWNWVGTIAADDDYGRPGIEKFREEAEERDICIDFSELISQYSD
EEEIQHVVEVIQNSTAKVIVVFSSGPDLEPLIKEIVRRNITGKIWLASEAWASSSLIAMP
QYFHVVGGTIGFALKAGQIPGFREFLKKVHPRKSVHNGFAKEFWEETFNCHLQEGAKGPL
PVDTFLRGHEESGDRFSNSSTAFRPLCTGDENISSVETPYIDYTHLRISYNVYLAVYSIA
HALQDIYTCLPGRGLFTNGSCADIKKVEAWQVLKHLRHLNFTNNMGEQVTFDECGDLVGN
YSIINWHLSPEDGSIVFKEVGYYNVYAKKGERLFINEEKILWSGFSREVPFSNCSRDCLA
GTRKGIIEGEPTCCFECVECPDGEYSDETDASACNKCPDDFWSNENHTSCIAKEIEFLSW
TEPFGIALTLFAVLGIFLTAFVLGVFIKFRNTPIVKATNRELSYLLLFSLLCCFSSSLFF
IGEPQDWTCRLRQPAFGISFVLCISCILVKTNRVLLVFEAKIPTSFHRKWWGLNLQFLLV
FLCTFMQIVICVIWLYTAPPSSYRNQELEDEIIFITCHEGSLMALGFLIGYTCLLAAICF
FFAFKSRKLPENFNEAKFITFSMLIFFIVWISFIPAYASTYGKFVSAVEVIAILAASFGL
LACIFFNKIYIILFKPSRNTIEEVRCSTAAHAFKVAARATLRRSNV

Sequence of entity 2 (C), FASTA

>8SZH_2 Guanine nucleotide-binding protein G(i) subunit alpha-3 (chains C)
MGCTLSAEDKAAVERSKMIDRNLREDGEKAAKEVKLLLLGAGESGKSTIVKQMKIIHEDG
YSEDECKQYKVVVYSNTIQSIIAIIRAMGRLKIDFGEAARADDARQLFVLAGSAEEGVMT
PELAGVIKRLWRDGGVQACFSRSREYQLNDSASYYLNDLDRISQSNYIPTQQDVLRTRVK
TTGIVETHFTFKDLYFKMFDVGGQRSERKKWIHCFEGVTAIIFCVALSDYDLVLAEDEEM
NRMHESMKLFDSICNNKWFTETSIILFLNKKDLFEEKIKRSPLTICYPEYTGSNTYEEAA
AYIQCQFEDLNRRKDTKEIYTHFTCATDTKNVQFVFDAVTDVIIKNNLKECGLY

Sequence of entity 3 (D), FASTA

>8SZH_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains D)
GSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAK
IYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGL
DNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQT
TTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPN
GNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVW
DALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 4 (E), FASTA

>8SZH_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains E)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

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
PCW	1,2-dioleoyl-sn-glycero-3-phosphocholine	C44 H85 N O8 P	2
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	3
CA	Calcium ion	Ca	4
TRP	Tryptophan	C11 H12 N2 O2	2
PO4	Phosphate ion	O4 P	2
SPM	Spermine	C10 H26 N4	4
CLR	Cholesterol	C27 H46 O	1

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
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

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