7T9I: Native human TSH

Native human TSH 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
Organisms: Homo sapiens, Lama glama
Chains: 7
Atoms: 11,972
Mol. weight: 198.81 kDa
Ligands: NAG
Released: 3 Aug 2022

Explore 7T9I in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7T9I contains 39 α-helices and 91 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: 2 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	9	1	1
β-strand	11-14	4	2
β-strand	20	1	3
β-strand	23	1	3
β-strand	26-29	4	2
β-strand	31-38	8	1
α-helix	39-40	2
α-helix	41-44	4
β-strand	53-57	5	1
β-strand	59-67	9	4
β-strand	77-85	9	4
β-strand	91	1	5

Chain B: 1 helix, 7 β-strands

Element	Residues	Length	Sheet
β-strand	3-11	9	1
β-strand	20-32	13	1
α-helix	44-47	4
β-strand	51-63	13	6
β-strand	74-86	13	6
β-strand	88	1	5
β-strand	93	1	1
β-strand	96	1	1

Chain N: 3 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	7
β-strand	11	1	8
β-strand	17-25	9	7
α-helix	29-31	3
β-strand	34-39	6	9
β-strand	46-51	6	9
β-strand	58-60	3	9
α-helix	62-64	3
β-strand	70-73	4	7
β-strand	78-84	7	7
α-helix	88-90	3
β-strand	92-98	7	9
β-strand	118	1	9
β-strand	122-124	3	9
β-strand	125	1	8

Chain R: 18 helices, 25 β-strands

Element	Residues	Length	Sheet
β-strand	30-33	4	10
β-strand	37-42	6	10
β-strand	56-60	5	10
β-strand	66-67	2	11
α-helix	68	1
β-strand	80-84	5	10
β-strand	91-92	2	11
β-strand	97-98	2	12
β-strand	105-111	7	10
β-strand	116-117	2	11
β-strand	122-123	2	12
β-strand	130-136	7	10
β-strand	149	1	13
β-strand	154-159	6	10
β-strand	166-167	2	14
α-helix	173-175	3
β-strand	176	1	13
β-strand	180-183	4	10
β-strand	191-192	2	14
β-strand	202-206	5	10
β-strand	215-216	2	14
α-helix	218-221	4
β-strand	230-232	3	10
β-strand	251-253	3	10
β-strand	274-276	3	10
α-helix	281-286	6
β-strand	290	1	15
α-helix	295-303	9
α-helix	381-390	10
β-strand	395	1	15
β-strand	397-399	3	10
α-helix	417-441	25
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	577-608	32
α-helix	620-648	29
α-helix	656-665	10
α-helix	669-675	7
α-helix	676-680	5
α-helix	683-696	14

Chain X: 8 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	15-39	25
β-strand	40-47	8	16
α-helix	53-58	6
β-strand	207	1	17
β-strand	210-214	5	16
β-strand	217-222	6	16
β-strand	224	1	17
α-helix	234-238	5
β-strand	243-249	7	16
α-helix	266-278	13
β-strand	287-292	6	16
α-helix	294-303	10
α-helix	313-316	4
α-helix	332-351	20
β-strand	359-363	5	16
α-helix	371-391	21

Chain Y: 3 helices, 29 β-strands

Element	Residues	Length	Sheet
α-helix	4-24	21
α-helix	30-33	4
α-helix	38-39	2
β-strand	47-51	5	18
β-strand	58-63	6	19
β-strand	69-74	6	19
β-strand	78-83	6	19
β-strand	88-89	2	19
β-strand	93-94	2	19
β-strand	100-105	6	20
β-strand	111-116	6	20
β-strand	120-125	6	20
β-strand	134-140	7	20
β-strand	146-151	6	21
β-strand	156-161	6	21
β-strand	166-170	5	21
β-strand	175-180	6	21
β-strand	187-192	6	22
β-strand	198-203	6	22
β-strand	207-212	6	22
β-strand	217-223	7	22
β-strand	231-234	4	23
β-strand	240-244	5	23
β-strand	250-254	5	23
β-strand	259-264	6	23
β-strand	273-278	6	24
β-strand	284-289	6	24
β-strand	294-298	5	24
β-strand	304-308	5	24
β-strand	317-320	4	18
β-strand	327-330	4	18
β-strand	336-339	4	18

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	56-58	3

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Glycoprotein hormones alpha chain	A	protein	92	Homo sapiens	P01215 (AlphaFold model)
Thyrotropin subunit beta	B	protein	112	Homo sapiens	P01222 (AlphaFold model)
Nanobody 35	N	protein	142	Lama glama
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
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	Z	protein	71	Homo sapiens	P59768

Sequence of entity 1 (A), FASTA

>7T9I_1 Glycoprotein hormones alpha chain (chains A)
APDVQDCPECTLQENPFFSQPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCC
VAKSYNRVTVMGGFKVENHTACHCSTCYYHKS

Sequence of entity 2 (B), FASTA

>7T9I_2 Thyrotropin subunit beta (chains B)
FCIPTEYTMHIERRECAYCLTINTTICAGYCMTRDINGKLFLPKYALSQDVCTYRDFIYR
TVEIPGCPLHVAPYFSYPVALSCKCGKCNTDYSDCIHEAIKTNYCTKPQKSY

Sequence of entity 3 (N), FASTA

>7T9I_3 Nanobody 35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSGSEDQVDPRLIDGK

Sequence of entity 4 (R), FASTA

>7T9I_4 Thyrotropin receptor (chains R)
DYKDDDDGTMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLRTIPSHAF
SNLPNISRIYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPDALKELPLLKFLG
IFNTGLKMFPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETLTLKLYNNGFTSV
QGYAFNGTKLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTALPSKGLEHLKEL
IARNTWTLKKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMCNESSMQSLRQR
KSVNGQELKNPQEETLQAFDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMGYKFLRIVVW
FVSLLALLGNVFVLLILLTSHYKLNVPRFLMCNLAFADFCMGMYLLLIASVDLYTHSEYY
NHAIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRKIRLRHACAIM
VGGWVCCFLLALLPLVGISSYAKVSICLPMDTETPLALAYIVFVLTLNIVAFVIVCCCYV
KIYITVRNPQYNPGDKDTKIAKRMAVLIFTDFICMAPISFYALSAILNKPLITVSNSKIL
LVLFYPLNSCANPFLYAIFTKAFQRDVFILLSKFGICKRQAQAYRGQRVPPKNSTDIQVQ
KVTHEMRQGLHNMEDVYELIENSHLTPKKQGQISEEYMQTVL

Sequence of entity 5 (X), FASTA

>7T9I_5 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains X)
GGSLEVLFQGPSGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGADNSG
KSTIVKQMRILHGGSGGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTA
IIFVVDSSDYNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKLEDYFP
EFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENAR
RIFNDCRDIIQRMHLRQYELL

Sequence of entity 6 (Y), FASTA

>7T9I_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

>7T9I_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	6

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 P01215 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9YXD 2.29 Å, Crystal structure of recombinant human follicle stimulating hormone in complex with an…
7UTZ 2.4 Å, Human thyrotropin analog TR1402 bound to human Thyrotropin receptor in complex with…
4AY9 2.5 Å, Structure of follicle-stimulating hormone in complex with the entire ectodomain of its…
1HCN 2.6 Å, Structure of human chorionic gonadotropin at 2.6 Å resolution from mad analysis of the…
8I2G 2.8 Å, FSHR-Follicle stimulating hormone-compound 716340-Gs complex
4MQW 2.9 Å, Structure of follicle-stimulating hormone in complex with the entire ectodomain of its…
1XWD 2.92 Å, Crystal Structure of Human Follicle Stimulating Hormone Complexed with its Receptor
7XW5 2.96 Å, TSHR-thyroid stimulating hormone-Gs-ML109 complex
1FL7 3.0 Å, Human follicle stimulating hormone
1HRP 3.0 Å, Crystal structure of human chorionic gonadotropin
7FIH 3.2 Å, luteinizing hormone/choriogonadotropin receptor(S277I)-chorionic…
1QFW 3.5 Å, Ternary complex of human chorionic gonadotropin with fv anti alpha subunit and fv anti…

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