7UTZ: Human thyrotropin analog TR1402

Human thyrotropin analog TR1402 bound to human Thyrotropin receptor in complex with miniGs399 (composite structure). Determined by electron microscopy at 2.4 Å resolution. Released 3 Aug 2022.

Method: Electron microscopy
Resolution: 2.4 Å
Organism: Homo sapiens
Chains: 7
Atoms: 12,047
Mol. weight: 199.22 kDa
Ligands: NAG, Z41
Released: 3 Aug 2022

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

Secondary structure: helices and β-sheets

7UTZ contains 41 α-helices and 92 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: 3 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	59-69	11	4
α-helix	71-73	3
β-strand	75-85	11	4
β-strand	91	1	5

Chain B: 1 helix, 6 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	93-96	4	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	45-51	7	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: 19 helices, 26 β-strands

Element	Residues	Length	Sheet
β-strand	30-33	4	10
β-strand	37-41	5	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	179-183	5	10
β-strand	191-192	2	14
β-strand	201-206	6	10
β-strand	215-216	2	14
α-helix	218-221	4
β-strand	226	1	10
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	295-304	10
α-helix	377-390	14
β-strand	395	1	15
β-strand	397-399	3	10
α-helix	401-402	2
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	669-674	6
α-helix	675-680	6
α-helix	683-696	14

Chain X: 8 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	15-39	25
β-strand	41-47	7	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, 30 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	88-94	7	19
β-strand	100-105	6	20
β-strand	111-116	6	20
β-strand	120	1	21
β-strand	121-125	5	20
β-strand	134-137	4	20
β-strand	140	1	21
β-strand	146-151	6	22
β-strand	156-161	6	22
β-strand	166-170	5	22
β-strand	175-180	6	22
β-strand	187-192	6	23
β-strand	198-203	6	23
β-strand	208-212	5	23
β-strand	218-222	5	23
β-strand	233-234	2	24
β-strand	240-243	4	24
β-strand	250-254	5	24
β-strand	259-264	6	24
β-strand	273-278	6	25
β-strand	284-289	6	25
β-strand	294-298	5	25
β-strand	304-308	5	25
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 analog TR1402	A	protein	92	Homo sapiens	P01215 (AlphaFold model)
Thyrotropin subunit beta	B	protein	112	Homo sapiens	P01222 (AlphaFold model)
Nanobody 35	N	protein	142	Homo sapiens
Thyrotropin receptor	R	protein	701	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

>7UTZ_1 Glycoprotein hormones alpha chain analog TR1402 (chains A)
APDVQDCPECTLRRNRFFSRPGAPILQCMGCCFSRAYPTPLRSKKTMLVQKNVTSESTCC
VAKSYNRVTVMGGFKVENHTACHCSTCYYHKS

Sequence of entity 2 (B), FASTA

>7UTZ_2 Thyrotropin subunit beta (chains B)
FCIPTEYTMHIERRECAYCLTINTTICAGYCMTRDINGKLFLPKYALSQDVCTYRDFIYR
TVEIPGCPLHVAPYFSYPVALSCKCGKCNTDYSDCIHEAIKTNYCTKPQKSY

Sequence of entity 3 (N), FASTA

>7UTZ_3 Nanobody 35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSGSEDQVDPRLIDGK

Sequence of entity 4 (R), FASTA

>7UTZ_4 Thyrotropin receptor (chains R)
DYKDDDDGMGCSSPPCECHQEEDFRVTCKDIQRIPSLPPSTQTLKLIETHLRTIPSHAFS
NLPNISRIYVSIDVTLQQLESHSFYNLSKVTHIEIRNTRNLTYIDPDALKELPLLKFLGI
FNTGLKMFPDLTKVYSTDIFFILEITDNPYMTSIPVNAFQGLCNETLTLKLYNNGFTSVQ
GYAFNGTKLDAVYLNKNKYLTVIDKDAFGGVYSGPSLLDVSQTSVTALPSKGLEHLKELI
ARNTWTLKKLPLSLSFLHLTRADLSYPSHCCAFKNQKKIRGILESLMCNESSMQSLRQRK
SVNGQELKNPQEETLQAFDSHYDYTICGDSEDMVCTPKSDEFNPCEDIMGYKFLRIVVWF
VSLLALLGNVFVLLILLTSHYKLNVPRFLMCNLAFADFCMGMYLLLIASVDLYTHSEYYN
HAIDWQTGPGCNTAGFFTVFASELSVYTLTVITLERWYAITFAMRLDRKIRLRHACAIMV
GGWVCCFLLALLPLVGISSYAKVSICLPMDTETPLALAYIVFVLTLNIVAFVIVCCCYVK
IYITVRNPQYNPGDKDTKIAKRMAVLIFTDFICMAPISFYALSAILNKPLITVSNSKILL
VLFYPLNSCANPFLYAIFTKAFQRDVFILLSKFGICKRQAQAYRGQRVPPKNSTDIQVQK
VTHEMRQGLHNMEDVYELIENSHLTPKKQGQISEEYMQTVL

Sequence of entity 5 (X), FASTA

>7UTZ_5 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains X)
GGSLEVLFQGPSGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGADNSG
KSTIVKQMRILHGGSGGSGGTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTA
IIFVVDSSDYNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKLEDYFP
EFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENAR
RIFNDCRDIIQRMHLRQYELL

Sequence of entity 6 (Y), FASTA

>7UTZ_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

>7UTZ_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	7
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 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…
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…
7T9I 2.9 Å, Native human TSH bound to human Thyrotropin receptor in complex with miniGs399…
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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