7XW6: TSHR-Gs-M22 antibody-ML109 complex

TSHR-Gs-M22 antibody-ML109 complex. Determined by electron microscopy at 2.78 Å resolution. Released 17 Aug 2022.

Method: Electron microscopy
Resolution: 2.78 Å
Organisms: Homo sapiens, Mus musculus
Chains: 7
Atoms: 12,881
Mol. weight: 204.81 kDa
Ligands: NAG, PLM, CLR, HOI
Released: 17 Aug 2022

Explore 7XW6 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7XW6 contains 50 α-helices and 95 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: 11 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	14-37	24
β-strand	40-46	7	1
α-helix	53-60	8
α-helix	61-63	3
β-strand	207-214	8	1
β-strand	217-224	8	1
α-helix	234-238	5
β-strand	243-249	7	1
α-helix	255-268	14
β-strand	277-282	6	1
α-helix	284-292	9
α-helix	297-300	4
α-helix	303-306	4
α-helix	314-316	3
α-helix	322-341	20
β-strand	349-353	5	1
α-helix	361-380	20

Chain B: 5 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	5-25	21
α-helix	30-34	5
α-helix	38-41	4
β-strand	47-51	5	2
α-helix	57	1
β-strand	58-63	6	3
β-strand	69-74	6	3
β-strand	78-83	6	3
β-strand	89-94	6	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	121-125	5	4
β-strand	134-139	6	4
β-strand	146-153	8	5
β-strand	156-161	6	5
β-strand	166-170	5	5
β-strand	175-180	6	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	207-212	6	6
β-strand	218-223	6	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	250-254	5	7
β-strand	259-264	6	7
α-helix	272	1
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	293-298	6	8
β-strand	304-309	6	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-339	4	2

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	8-23	16
α-helix	30-43	14
α-helix	45-47	3
α-helix	53-55	3

Chain L: 2 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	4	1	9
β-strand	5	1	10
β-strand	9-13	4	11
β-strand	19-24	6	10
α-helix	27-29	5
β-strand	34-38	5	11
β-strand	45-48	4	11
β-strand	49	1	12
β-strand	53	1	12
β-strand	62-67	6	10
β-strand	70-75	6	10
α-helix	80-82	3
β-strand	85-92	8	11
β-strand	95B-98	4	11
β-strand	99	1	9
β-strand	102-106	5	11

Chain N: 3 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-8	6	13
β-strand	10-12	3	14
β-strand	18-25	8	13
α-helix	29-31	3
β-strand	34-39	6	14
β-strand	46-51	6	14
β-strand	58-60	3	14
α-helix	62-64	3
β-strand	68-73	6	13
β-strand	78-83	6	13
α-helix	88-90	3
β-strand	92-98	7	14
β-strand	118	1	14
β-strand	122-126	5	14

Chain R: 22 helices, 24 β-strands

Element	Residues	Length	Sheet
β-strand	29-33	5	15
β-strand	37-41	5	15
α-helix	47-49	3
β-strand	54-62	9	15
β-strand	66-67	2	16
α-helix	68	1
β-strand	80-86	7	15
β-strand	91-92	2	16
β-strand	97-98	2	17
β-strand	105-111	7	15
β-strand	116-117	2	16
β-strand	122-123	2	17
β-strand	130-136	7	15
β-strand	149	1	18
β-strand	153-159	7	15
β-strand	166-167	2	19
α-helix	168	1
β-strand	176	1	18
β-strand	179-183	5	15
β-strand	191-192	2	19
β-strand	201-206	6	15
β-strand	215-216	2	19
β-strand	226	1	15
β-strand	230-232	3	15
β-strand	251-253	3	15
α-helix	266-269	4
β-strand	274-276	3	15
α-helix	282-289	8
β-strand	397-399	3	15
α-helix	401-403	3
α-helix	415-429	15
α-helix	432-441	10
α-helix	445-447	3
α-helix	448-477	30
α-helix	481-483	3
α-helix	485-490	6
α-helix	492-524	33
α-helix	529-531	3
α-helix	532-534	3
α-helix	535-558	24
α-helix	577-608	32
α-helix	618-648	31
α-helix	659-665	7
α-helix	669-675	7
α-helix	676-680	5
α-helix	683-693	11

Chain Y: 3 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	20
α-helix	7-9	3
β-strand	10-12	3	21
β-strand	18-25	8	20
α-helix	29-31	3
β-strand	33-39	7	21
β-strand	46-52	7	21
β-strand	56-59	4	21
β-strand	64	1	20
β-strand	67-72	6	20
β-strand	77-82	6	20
α-helix	84-86	3
β-strand	88-95	8	21
β-strand	100D-103	4	21
β-strand	107-111	5	21

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	249	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	350	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)
M22 antibody light chain	L	protein	112	Mus musculus
Nanobody35	N	protein	134	Homo sapiens
Thyrotropin receptor	R	protein	702	Homo sapiens	P16473 (AlphaFold model)
M22 antibody heavy chain	Y	protein	120	Homo sapiens

Sequence of entity 1 (A), FASTA

>7XW6_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRILH
GGSGGSGGTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNR
LQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDAT
PEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRIFNDCRDIIQR
MHLRQYELL

Sequence of entity 2 (B), FASTA

>7XW6_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
HHHHHHGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRT
LRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGN
YVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWD
IETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDIN
AICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYD
DFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>7XW6_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (L), FASTA

>7XW6_4 M22 antibody light chain (chains L)
LTVLTQPPSVSGAPRQRVTISCSGNSSNIGNNAVNWYQQLPGKAPKLLIYYDDQLPSGVS
DRFSGSRSGTSASLAIRGLQSEDEADYYCTSWDDSLDSQLFGGGTRLTVLGQ

Sequence of entity 5 (N), FASTA

>7XW6_5 Nanobody35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSHHHHHH

Sequence of entity 6 (R), FASTA

>7XW6_6 Thyrotropin receptor (chains R)
GMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLRTIPSHAFSNLPNISR
IYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPDALKELPLLKFLGIFNTGLKM
FPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETLTLKLYNNGFTSVQGYAFNGT
KLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTALPSKGLEHLKELIARNTWTL
KKLPLSLSFLHLTRADLSYPIHCCAFKNQKKIRGILESLMCNESSMQSLRQRKSVNNKTL
KNPQEETLQAFDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMGYKFLRIVVWFVSLLALL
GNVFVLLILLTSHYKLNVPRFLMCNLAFADFCMGMYLLLIASVDLYTHSEYYNHAIDWQT
GPGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRKIRLRHACAIMVGGWVCCF
LLALLPLVGISSYAKVSICLPMDTETPLALAYIVFVLTLNIVAFVIVCCCYVKIYITVRN
PQYNPGDKDTKIAKRMAVLIFTDFICMAPISFYALSAILNKPLITVSNSKILLVLFYPLN
SCANPFLYAIFTKAFQRDVFILLSKFGICKRQAQAYRGQRVPPKNSTDIQVQKVTHDMRQ
GLHNMEDVYELIENSHLTPKKQGQISEEYMQTVLHHHHHHHH

Sequence of entity 7 (Y), FASTA

>7XW6_7 M22 antibody heavy chain (chains Y)
QVQLVQSGAEVKKPGESLKISCRGSGYRFTSYWINWVRQLPGKGLEWMGRIDPTDSYTNY
SPSFKGHVTVSADKSINTAYLQWSSLKASDTGMYYCARLEPGYSSTWSVNWGQGTLVTVS

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	4
PLM	Palmitic acid	C16 H32 O2	5
CLR	Cholesterol	C27 H46 O	17
HOI	~{N}-[4-[[2-methoxy-5-[(2~{S})-5-oxidanyl-4-oxidanylidene-3-(phenylmethyl)-1,2-…	C31 H29 N3 O5	1

Primary citation

Hormone- and antibody-mediated activation of the thyrotropin receptor. Duan, J., Xu, P., Luan, X. et al. Nature (2022) 609:854-859. DOI 10.1038/s41586-022-05173-3 · PubMed

Other PDB entries of the same protein (UniProt P63092 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7BPH 1.57 Å, Crystal structure of GppNHp-bound GNAS in complex with the cyclic peptide inhibitor GN13
6AU6 1.7 Å, Crystal structure of GDP-bound human GNAS R201C mutant
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
7E5E 1.95 Å, Crystal structure of GDP-bound GNAS in complex with the cyclic peptide inhibitor GD20
7MBX 1.95 Å, Human Cholecystokinin 1 receptor (CCK1R) Gs complex
8F0J 2.0 Å, Calcitonin Receptor in complex with Gs and Pramlintide analogue peptide San45
8F2B 2.0 Å, Amylin 3 Receptor in complex with Gs and Pramlintide analogue peptide San45
9XXT 2.0 Å, Cryo-EM structure of lysophosphatidylserine (18:0)-bound GPR174-Gs complex
6X18 2.1 Å, GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Receptor
6X19 2.1 Å, Non peptide agonist CHU-128, bound to Glucagon-Like peptide-1 (GLP-1) Receptor
9NTU 2.1 Å, Cryo-EM structure of BETP-GLP-1(9-36)-GLP-1R-Gs complex
7RTB 2.14 Å, Peptide-19 bound to the Glucagon-Like Peptide-1 Receptor (GLP-1R)

Browse structure collections

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