8F0K: Human Amylin3 Receptor

Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385. Determined by electron microscopy at 1.9 Å resolution. Released 2 Aug 2023.

Method: Electron microscopy
Resolution: 1.9 Å
Organisms: Homo sapiens, Lama glama
Chains: 7
Atoms: 10,553
Mol. weight: 192.21 kDa
Ligands: P42, NAG, PTY, Y01
Released: 2 Aug 2023

Explore 8F0K in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8F0K contains 53 α-helices and 61 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	12-39	28
β-strand	41-47	7	8
α-helix	53-59	7
β-strand	207-214	8	8
β-strand	217-224	8	8
α-helix	234-238	5
β-strand	243-249	7	8
α-helix	265-277	13
β-strand	286-292	7	8
α-helix	294-303	10
α-helix	313-315	3
α-helix	326-327	2
α-helix	332-349	18
β-strand	359-363	5	8
α-helix	371-390	20

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	3-25	23
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-52	6	9
β-strand	58-63	6	10
β-strand	69-74	6	10
β-strand	78-83	6	10
β-strand	89-94	6	10
β-strand	100-105	6	11
β-strand	111-116	6	11
β-strand	121-125	5	11
β-strand	134-139	6	11
β-strand	146-151	6	12
β-strand	156-161	6	12
β-strand	166-170	5	12
β-strand	175-180	6	12
β-strand	187-192	6	13
β-strand	198-203	6	13
β-strand	207-212	6	13
β-strand	218-223	6	13
β-strand	229-234	6	14
β-strand	240-245	6	14
β-strand	250-254	5	14
β-strand	259-264	6	14
β-strand	273-278	6	15
β-strand	284-289	6	15
β-strand	294-298	5	15
β-strand	304-308	5	15
β-strand	315-320	6	9
β-strand	327-331	5	9
β-strand	335-339	5	9

Chain E: 8 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	30-47	18
α-helix	53-56	4
α-helix	59-79	21
α-helix	87-100	14
α-helix	104-109	6
β-strand	111	1	1
α-helix	113-115	3
α-helix	116-119	4
α-helix	121-140	20

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	9-23	15
α-helix	30-44	15
α-helix	45-47	3
α-helix	53-55	3

Chain N: 2 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	16
β-strand	11-12	2	17
β-strand	18-25	8	16
α-helix	29-31	3
β-strand	34-39	6	18
β-strand	45-51	7	18
β-strand	58-60	3	18
β-strand	68-73	6	16
β-strand	78-83	6	16
α-helix	88-90	3
β-strand	92-98	7	18
β-strand	118	1	18
β-strand	122-124	3	18
β-strand	125-126	2	17

Chain P: 4 helices, 1 β-strand

Element	Residues	Length	Sheet
β-strand	4	1	2
α-helix	5-7	3
α-helix	8-18	11
α-helix	21-23	3
α-helix	25-31	7

Chain R: 23 helices, 13 β-strands

Element	Residues	Length	Sheet
α-helix	42-61	20
α-helix	63-65	3
β-strand	71-72	2	3
α-helix	73-74	2
β-strand	75-76	2	4
β-strand	81-82	2	4
β-strand	85-86	2	3
β-strand	90-94	5	5
β-strand	107-111	5	5
β-strand	112	1	6
β-strand	118	1	6
β-strand	120	1	7
β-strand	127	1	7
β-strand	130	1	5
α-helix	132-134	3
α-helix	138-172	35
α-helix	174-176	3
α-helix	179-200	22
α-helix	201-205	5
α-helix	209-214	6
α-helix	217-245	29
α-helix	246-250	5
α-helix	260-263	4
α-helix	264-268	5
α-helix	271-283	13
β-strand	285	1	1
α-helix	288-290	3
α-helix	296-298	3
α-helix	299-329	31
α-helix	334-352	19
α-helix	355-358	4
β-strand	361	1	2
α-helix	366-381	16
α-helix	383-388	6
α-helix	389-393	5
α-helix	396-405	10

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Receptor activity-modifying protein 3	E	protein	149	Homo sapiens	O60896 (AlphaFold model)
San385	P	protein	38	Homo sapiens	P10997 (AlphaFold model)
Calcitonin receptor	R	protein	501	Homo sapiens	P30988 (AlphaFold model)
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	394	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	350	Homo sapiens	P62873
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768
Nanobody 35	N	protein	138	Lama glama

Sequence of entity 1 (E), FASTA

>8F0K_1 Receptor activity-modifying protein 3 (chains E)
MKTIIALSYIFCLVFADYKDDDDKRAGGCNETGMLERLPLCGKAFADMMGKVDVWKWCNL
SEFIVYYESFTNCTEMEANVVGCYWPNPLAQGFITGIHRQFFSNCTVDRVHLEDPPDEVL
IPLIVIPVVLTVAMAGLVVWRSKRTDTLL

Sequence of entity 2 (P), FASTA

>8F0K_2 San385 (chains P)
KCNTATCATQRLANFLVHKSNNFGPILPPTNVGSNTYX

Sequence of entity 3 (R), FASTA

>8F0K_3 Calcitonin receptor (chains R)
MKTIIALSYIFCLVFADYKDDDDLEVLFQGPAAFSNQTYPTIEPKPFLYVVGRKKMMDAQ
YKCYDRMQQLPAYQGEGPYCNRTWDGWLCWDDTPAGVLSYQFCPDYFPDFDPSEKVTKYC
DEKGVWFKHPENNRTWSNYTMCNAFTPEKLKNAYVLYYLAIVGHSLSIFTLVISLGIFVF
FRSLGCQRVTLHKNMFLTYILNSMIIIIHLVEVVPNGELVRRDPVSCKILHFFHQYMMAC
NYFWMLCEGIYLHTLIVVAVFTEKQRLRWYYLLGWGFPLVPTTIHAITRAVYFNDNCWLS
VETHLLYIIHGPVMAALVVNFFFLLNIVRVLVTKMRETHEAESHMYLKAVKATMILVPLL
GIQFVVFPWRPSNKMLGKIYDYVMHSLIHFQGFFVATIYCFCNNEVQTTVKRQWAQFKIQ
WNQRWGRRPSNRSARAAAAAAEAGDIPIYICHQELRNEPANNQGEESAEIIPLNIIEQES
SAPAGLEVLFQGPHHHHHHHH

Sequence of entity 4 (A), FASTA

>8F0K_4 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 5 (B), FASTA

>8F0K_5 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MHHHHHHGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRT
LRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGN
YVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWD
IETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDIN
AICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYD
DFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 6 (G), FASTA

>8F0K_6 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 7 (N), FASTA

>8F0K_7 Nanobody 35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSHHHHHHEPEA

Ligands and cofactors

ID	Name	Formula	Copies
P42	(2S)-2-{[(1R)-1-hydroxyhexadecyl]oxy}-3-{[(1R)-1-hydroxyoctadecyl]oxy}propyl…	C42 H88 N O8 P	1
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	5
PTY	Phosphatidylethanolamine	C40 H80 N O8 P	1
Y01	Cholesterol hemisuccinate	C31 H50 O4	2
PLM	Palmitic acid	C16 H32 O2	8

Primary citation

Structural insight into selectivity of amylin and calcitonin receptor agonists. Cao, J., Belousoff, M.J., Gerrard, E. et al. Nat Chem Biol (2024) 20:162-169. DOI 10.1038/s41589-023-01393-4 · PubMed

Other PDB entries of the same protein (UniProt O60896 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8F2B 2.0 Å, Amylin 3 Receptor in complex with Gs and Pramlintide analogue peptide San45
8F2A 2.2 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385…
6UVA 2.3 Å, CryoEM Structure of the active Adrenomedullin 2 receptor G protein complex with…
6UUS 2.4 Å, CryoEM Structure of the active Adrenomedullin 2 receptor G protein complex with…
7TZF 2.4 Å, Human Amylin3 Receptor in complex with Gs and rat amylin peptide
9BTW 3.0 Å, Human Amylin3 Receptor in complex with Gs and cagrilintide

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