7T9N: M22 Agonist Autoantibody

M22 Agonist Autoantibody bound to Human Thyrotropin receptor in complex with miniGs399 (composite structure). Determined by electron microscopy at 2.9 Å resolution. Released 3 Aug 2022.

Method: Electron microscopy
Resolution: 2.9 Å
Organism: Homo sapiens
Chains: 7
Atoms: 13,389
Mol. weight: 227.41 kDa
Ligands: NAG, Z41
Released: 3 Aug 2022

Explore 7T9N in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7T9N contains 54 α-helices and 118 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 H: 8 helices, 23 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	7
β-strand	10	1	8
α-helix	12-13	2
β-strand	18-25	8	7
α-helix	29-31	3
β-strand	34-39	6	8
β-strand	45-52	8	8
β-strand	56-59	4	8
β-strand	64	1	7
β-strand	67-72	6	7
α-helix	73-75	3
β-strand	77-82	6	7
α-helix	84-86	3
β-strand	88-95	8	8
α-helix	96	1
β-strand	100D-103	4	8
β-strand	107-109	3	8
β-strand	117	1	9
β-strand	120-124	5	10
β-strand	135-145	11	10
β-strand	146	1	9
β-strand	151-154	4	11
α-helix	155-157	3
β-strand	159	1	11
β-strand	163-165	3	10
α-helix	166-168	3
β-strand	169-170	2	10
β-strand	176-185	10	10
α-helix	186-189	4
β-strand	194-200	7	11
β-strand	205-211	7	11

Chain L: 9 helices, 22 β-strands

Element	Residues	Length	Sheet
β-strand	5	1	1
β-strand	9-13	4	2
β-strand	19-24	6	1
α-helix	27B-29	3
β-strand	34-38	5	2
β-strand	45-48	4	2
β-strand	49	1	3
β-strand	53	1	3
α-helix	54-55	2
β-strand	62-67	6	1
β-strand	70-75	6	1
α-helix	80-82	3
β-strand	85-92	8	2
β-strand	95B-98	4	2
α-helix	99	1
β-strand	102-106	5	2
β-strand	112	1	4
α-helix	113-114	2
β-strand	115-119	5	5
α-helix	120-122	3
α-helix	123-126	4
β-strand	131-140	10	5
β-strand	141	1	4
β-strand	145-149	5	6
β-strand	156	1	6
β-strand	160-162	3	5
α-helix	163-165	3
β-strand	173-181	9	5
α-helix	183-187	5
β-strand	192-198	7	6
β-strand	201-207	7	6

Chain N: 4 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	12
β-strand	11	1	13
β-strand	18-25	8	12
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	69-73	5	12
α-helix	74-76	3
β-strand	78-83	6	12
α-helix	88-90	3
β-strand	92-98	7	14
β-strand	118	1	14
β-strand	122-124	3	14
β-strand	125	1	13

Chain R: 18 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	30-32	3	15
β-strand	38-41	4	15
β-strand	56-60	5	15
β-strand	66-67	2	16
β-strand	80-84	5	15
β-strand	91-92	2	16
α-helix	93	1
β-strand	97-98	2	17
β-strand	105-109	5	15
β-strand	116-117	2	16
β-strand	122-123	2	17
β-strand	130-134	5	15
β-strand	149	1	18
β-strand	153-159	7	15
β-strand	166-167	2	19
β-strand	173	1	18
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
α-helix	218-220	3
β-strand	226	1	15
β-strand	230-232	3	15
α-helix	246-248	3
β-strand	251-253	3	15
β-strand	274-276	3	15
α-helix	280-286	7
β-strand	397-398	2	15
α-helix	415-441	27
α-helix	448-476	29
α-helix	481-490	10
α-helix	492-524	33
α-helix	529-531	3
α-helix	535-558	24
α-helix	563-565	3
α-helix	577-608	32
α-helix	620-648	29
α-helix	656-661	6
α-helix	662-666	5
α-helix	669-675	7
α-helix	676-680	5
α-helix	683-695	13

Chain X: 8 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	15-39	25
β-strand	41-47	7	20
α-helix	53-60	8
β-strand	207-214	8	20
β-strand	217-224	8	20
α-helix	234-238	5
β-strand	243-249	7	20
α-helix	266-278	13
β-strand	287-292	6	20
α-helix	294-302	9
α-helix	313-317	5
α-helix	332-351	20
β-strand	359-362	4	20
α-helix	371-391	21

Chain Y: 3 helices, 30 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	21
β-strand	58-63	6	22
β-strand	69-74	6	22
β-strand	78-83	6	22
β-strand	88-94	7	22
β-strand	100-105	6	23
β-strand	111-116	6	23
β-strand	120-125	6	23
β-strand	134-140	7	23
β-strand	146-151	6	24
β-strand	156-161	6	24
β-strand	165-170	6	24
β-strand	175-181	7	24
β-strand	187-192	6	25
β-strand	198-203	6	25
β-strand	208-212	5	25
β-strand	217-222	6	25
β-strand	229-234	6	26
β-strand	240-245	6	26
β-strand	250-254	5	26
β-strand	259-264	6	26
β-strand	273-278	6	27
β-strand	284-289	6	27
β-strand	294-298	5	27
β-strand	304-308	5	27
β-strand	315	1	28
β-strand	319-320	2	21
β-strand	327-330	4	21
β-strand	331	1	28
β-strand	336-339	4	21

Chain Z: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	8-23	16
α-helix	30-44	15
α-helix	45-47	3
α-helix	53-55	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
M22 Fab light chain	L	protein	234	Homo sapiens
M22 Fab heavy chain	H	protein	252	Homo sapiens
Nanobody 35	N	protein	142	Homo sapiens
Thyrotropin receptor	R	protein	702	Homo sapiens	P16473 (AlphaFold model)
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	X	protein	261	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	Y	protein	370	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	Z	protein	71	Homo sapiens	P59768 (AlphaFold model)

Sequence of entity 1 (L), FASTA

>7T9N_1 M22 Fab light chain (chains L)
DYKDDDDKLEVLFQGPGSLTVLTQPPSVSGAPRQRVTISCSGNSSNIGNNAVNWYQQLPG
KAPKLLIYYDDQLPSGVSDRFSGSRSGTSASLAIRGLQSEDEADYYCTSWDDSLDSQLFG
GGTRLTVLGQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAG
VETTTPSKQSNNKYAASSYLSLTPEQWKSHKSYSCQVTHEGSTVEKTVAPTECS

Sequence of entity 2 (H), FASTA

>7T9N_2 M22 Fab heavy chain (chains H)
QVQLVQSGAEVKKPGESLKISCRGSGYRFTSYWINWVRQLPGKGLEWMGRIDPTDSYTNY
SPSFKGHVTVSADKSINTAYLQWSSLKASDTGMYYCARLEPGYSSTWSVNWGQGTLVTVS
SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQS
SGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTSLEVLFQGPAAAL
PETGHHHHHHHH

Sequence of entity 3 (N), FASTA

>7T9N_3 Nanobody 35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSGSEDQVDPRLIDGK

Sequence of entity 4 (R), FASTA

>7T9N_4 Thyrotropin receptor (chains R)
DYKDDDDGTMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLRTIPSHAF
SNLPNISRIYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPDALKELPLLKFLG
IFNTGLKMFPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETLTLKLYNNGFTSV
QGYAFNGTKLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTALPSKGLEHLKEL
IARNTWTLKKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMCNESSMQSLRQR
KSVNGQELKNPQEETLQAFDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMGYKFLRIVVW
FVSLLALLGNVFVLLILLTSHYKLNVPRFLMCNLAFADFCMGMYLLLIASVDLYTHSEYY
NHAIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRKIRLRHACAIM
VGGWVCCFLLALLPLVGISSYAKVSICLPMDTETPLALAYIVFVLTLNIVAFVIVCCCYV
KIYITVRNPQYNPGDKDTKIAKRMAVLIFTDFICMAPISFYALSAILNKPLITVSNSKIL
LVLFYPLNSCANPFLYAIFTKAFQRDVFILLSKFGICKRQAQAYRGQRVPPKNSTDIQVQ
KVTHEMRQGLHNMEDVYELIENSHLTPKKQGQISEEYMQTVL

Sequence of entity 5 (X), FASTA

>7T9N_5 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains X)
GGSLEVLFQGPSGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGADNSG
KSTIVKQMRILHGGSGGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTA
IIFVVDSSDYNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKLEDYFP
EFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENAR
RIFNDCRDIIQRMHLRQYELL

Sequence of entity 6 (Y), FASTA

>7T9N_6 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains Y)
MHHHHHHLEVLFQGPEDQVDPRLIDGKGSSGSELDQLRQEAEQLKNQIRDARKACADATL
SQITNNIDPVGRIQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKV
HAIPLRSSWVMTCAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCR
FLDDNQIVTSSGDTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKL
WDVREGMCRQTFTGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNII
CGITSVSFSKSGRLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATG
SWDSFLKIWN

Sequence of entity 7 (Z), FASTA

>7T9N_7 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains Z)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Ligands and cofactors

ID	Name	Formula	Copies
NAG	2-acetamido-2-deoxy-beta-D-glucopyranose	C8 H15 N O6	3
Z41	(2S)-3-hydroxypropane-1,2-diyl dihexadecanoate	C35 H68 O5	1

Primary citation

Autoantibody mimicry of hormone action at the thyrotropin receptor. Faust, B., Billesbolle, C.B., Suomivuori, C.M. et al. Nature (2022) 609:846-853. DOI 10.1038/s41586-022-05159-1 · PubMed

Other PDB entries of the same protein (UniProt P16473 (AlphaFold model), which also has an AlphaFold model), best resolution first:

2XWT 1.9 Å, Crystal structure of the tsh receptor in complex with a blocking type tshr autoantibody
7UTZ 2.4 Å, Human thyrotropin analog TR1402 bound to human Thyrotropin receptor in complex with…
3G04 2.55 Å, Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody
7XW6 2.78 Å, TSHR-Gs-M22 antibody-ML109 complex
7T9I 2.9 Å, Native human TSH bound to human Thyrotropin receptor in complex with miniGs399…
7XW5 2.96 Å, TSHR-thyroid stimulating hormone-Gs-ML109 complex
7T9M 3.1 Å, Human Thyrotropin receptor bound by CS-17 Inverse Agonist Fab/Org 274179-0 Antagonist
7XW7 5.5 Å, TSHR-K1-70 complex

Browse structure collections

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