7STH: Full-length insulin receptor

Full-length insulin receptor bound with unsaturated insulin WT (2 insulin bound) symmetric conformation. Determined by electron microscopy at 3.5 Å resolution. Released 30 Mar 2022.

Method: Electron microscopy
Resolution: 3.5 Å
Organisms: Mus musculus, Homo sapiens
Chains: 4
Atoms: 14,010
Mol. weight: 335.56 kDa
Released: 30 Mar 2022

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

Secondary structure: helices and β-sheets

7STH contains 56 α-helices and 157 β-strands across 4 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: 23 helices, 77 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	1
β-strand	11-13	3	2
α-helix	19-22	4
β-strand	26	1	1
β-strand	28-29	2	3
β-strand	33-38	6	2
α-helix	44-47	4
β-strand	56-57	2	3
β-strand	61-66	6	2
β-strand	71	1	4
β-strand	81-82	2	3
β-strand	91-96	6	2
β-strand	103	1	4
β-strand	111-112	2	3
β-strand	116-122	7	2
α-helix	133-135	3
β-strand	137	1	3
β-strand	144-148	5	2
α-helix	149-152	4
β-strand	171-173	3	5
β-strand	178-180	3	5
β-strand	182-184	3	6
β-strand	187-188	2	6
α-helix	191-193	3
β-strand	201	1	7
β-strand	207	1	7
β-strand	212	1	8
β-strand	216	1	9
α-helix	222-224	3
β-strand	225	1	9
β-strand	228	1	8
β-strand	232-233	2	10
β-strand	236-237	2	10
α-helix	241-242	2
β-strand	246-248	3	11
β-strand	252-254	3	11
α-helix	256-267	12
β-strand	279	1	12
β-strand	280	1	11
β-strand	283-284	2	11
β-strand	292-294	3	13
β-strand	300	1	12
β-strand	301-303	3	13
α-helix	304	1
β-strand	311-312	2	14
α-helix	315-317	3
β-strand	319-321	3	15
α-helix	324-327	4
α-helix	328-330	3
β-strand	335-336	2	14
β-strand	340-342	3	15
α-helix	351-357	7
β-strand	363-364	2	14
β-strand	368-371	4	15
β-strand	378	1	16
β-strand	387-388	2	14
β-strand	394	1	17
β-strand	398	1	17
β-strand	400-403	4	15
β-strand	410	1	16
β-strand	420-421	2	14
β-strand	425	1	17
β-strand	428-429	2	15
α-helix	436-446	11
β-strand	457	1	15
β-strand	472-473	2	18
β-strand	475	1	19
β-strand	479-480	2	20
β-strand	485-487	3	20
β-strand	489	1	19
α-helix	497-499	3
β-strand	500-509	10	18
β-strand	530-534	5	18
β-strand	551-552	2	20
β-strand	561-570	10	18
β-strand	582-583	2	18
β-strand	586-589	4	18
α-helix	596-598	3
β-strand	599-607	9	21
β-strand	610-616	7	21
β-strand	627-631	5	22
β-strand	634-635	2	22
α-helix	636-638	3
α-helix	639-642	4
α-helix	688-689	2
α-helix	690-714	25
β-strand	760-763	4	22
β-strand	768-771	4	21
β-strand	779-787	9	22
β-strand	800-804	5	22
β-strand	820-823	4	23
β-strand	829-832	4	23
β-strand	843-852	10	24
β-strand	858-863	6	24
α-helix	864-870	7
β-strand	873-875	3	23
α-helix	878-879	2
β-strand	882-891	10	24
α-helix	895-898	4
β-strand	902-905	4	24

Chain B: 25 helices, 76 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	25
β-strand	11-13	3	26
α-helix	20-22	3
β-strand	26	1	25
β-strand	28-29	2	27
β-strand	33-38	6	26
α-helix	44-47	4
β-strand	56-57	2	27
β-strand	61-66	6	26
β-strand	71	1	28
β-strand	81-82	2	27
β-strand	91-96	6	26
β-strand	103	1	28
β-strand	111-112	2	27
β-strand	116-122	7	26
α-helix	133-135	3
β-strand	137	1	27
β-strand	144-148	5	26
α-helix	149-152	4
β-strand	171-173	3	29
β-strand	178-180	3	29
β-strand	182-184	3	30
β-strand	187-188	2	30
α-helix	191-193	3
β-strand	201	1	31
β-strand	207	1	31
β-strand	212	1	32
β-strand	216	1	33
α-helix	222-224	3
β-strand	225	1	33
β-strand	228	1	32
β-strand	231-232	2	34
β-strand	237-238	2	34
α-helix	241-242	2
α-helix	245	1
β-strand	246-248	3	35
β-strand	252-254	3	35
α-helix	256-267	12
β-strand	279	1	36
β-strand	283-284	2	35
β-strand	292-294	3	37
β-strand	300	1	36
β-strand	301-303	3	37
α-helix	304	1
β-strand	311-312	2	38
α-helix	315-317	3
β-strand	319-321	3	39
α-helix	324-327	4
α-helix	328-330	3
β-strand	335-336	2	38
β-strand	340-342	3	39
α-helix	351-357	7
β-strand	363-364	2	38
β-strand	368-371	4	39
β-strand	378	1	40
β-strand	387-388	2	38
β-strand	394	1	41
β-strand	398	1	41
β-strand	400-403	4	39
β-strand	410	1	40
β-strand	420-421	2	38
β-strand	425	1	41
β-strand	428-429	2	39
α-helix	436-446	11
β-strand	457	1	39
β-strand	472-473	2	42
β-strand	475	1	43
β-strand	479-480	2	44
β-strand	485-487	3	44
β-strand	489	1	43
α-helix	497-499	3
β-strand	500-509	10	42
β-strand	530-534	5	42
β-strand	551-552	2	44
β-strand	561-570	10	42
β-strand	582-583	2	42
β-strand	586-589	4	42
α-helix	596-598	3
β-strand	599-604	6	45
β-strand	611-616	6	45
α-helix	617-618	2
β-strand	627-634	8	46
α-helix	636-638	3
α-helix	639-643	5
α-helix	693-714	22
β-strand	760-763	4	46
β-strand	768-771	4	45
β-strand	779-787	9	46
β-strand	800-805	6	46
α-helix	806-808	3
β-strand	820-823	4	47
β-strand	828-832	5	47
β-strand	843-852	10	48
β-strand	858-863	6	48
α-helix	864-870	7
β-strand	873-876	4	47
α-helix	878-879	2
β-strand	882-891	10	48
β-strand	895	1	48
α-helix	896-898	3
β-strand	902-905	4	48

Chain C: 4 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	9-18	10
β-strand	24	1	49
α-helix	58	1
α-helix	59-63	5
α-helix	68-71	4
β-strand	75	1	49

Chain D: 4 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	9-18	10
β-strand	24	1	50
α-helix	58	1
α-helix	59-63	5
α-helix	69-71	3
β-strand	75	1	50

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Insulin receptor	A, B	protein	1372	Mus musculus	P15208 (AlphaFold model)
Insulin	C, D	protein	110	Homo sapiens	P01308 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7STH_1 Insulin receptor (chains A, B)
MGFGRGCETTAVPLLVAVAALLVGTAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHL
QILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYAL
VIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNE
ECGDVCPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHKECL
GNCSEPDDPTKCVACRNFYLDGQCVETCPPPYYHFQDWRCVNFSFCQDLHFKCRNSRKPG
CHQYVIHNNKCIPECPSGYTMNSSNLMCTPCLGPCPKVCQILEGEKTIDSVTSAQELRGC
TVINGSLIINIRGGNNLAAELEANLGLIEEISGFLKIRRSYALVSLSFFRKLHLIRGETL
EIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQE
RNDIALKTNGDQASCENELLKFSFIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQ
NVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPGWLMRGLKPWTQYAIFVKTLVT
FSDERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVY
WERQAEDSELFELDYCLKGLKLPSRTWSPPFESDDSQKHNQSEYDDSASECCSCPKTDSQ
ILKELEESSFRKTFEDYLHNVVFVPRPSRKRRSLEEVGNVTATTLTLPDFPNVSSTIVPT
SQEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDSPDERCSVAAYVSARTMPEAKA
DDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERG
CRLRGLSPGNYSVRVRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSV
VIGSIYLFLRKRQPDGPMGPLYASSNPEYLSASDVFPSSVYVPDEWEVPREKITLLRELG
QGSFGMVYEGNAKDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLL
GVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAENNPGRPPPTLQEMIQMTAEIADGMAYL
NAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMSPESLKD
GVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDPPDNCPERLTDLMR
MCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFYSEENKAPESEELEMEFEDMENVPLD
RSSHCQREEAGGREGGSSLSIKRTYDEHIPYTHMNGGKKNGRVLTLPRSNPS

Sequence of entity 2 (C, D), FASTA

>7STH_2 Insulin (chains C, D)
MALWMRLLPLLALLALWGPDPAAAFVNQHLCGSHLVEALYLVCGERGFFYTPKTRREAED
LQVGQVELGGGPGAGSLQPLALEGSLQKRGIVEQCCTSICSLYQLENYCN

Primary citation

Synergistic activation of the insulin receptor via two distinct sites. Li, J., Park, J., Mayer, J.P. et al. Nat Struct Mol Biol (2022) 29:357-368. DOI 10.1038/s41594-022-00750-6 · PubMed

Other PDB entries of the same protein (UniProt P15208 (AlphaFold model), which also has an AlphaFold model), best resolution first:

1LK2 1.35 Å, 1.35A crystal structure of H-2Kb complexed with the GNYSFYAL peptide
7SL7 3.1 Å, Full-length insulin receptor bound with both site 1 binding deficient mutant insulin…
7SL1 3.4 Å, Full-length insulin receptor bound with site 1 binding deficient mutant insulin (A-V3E)
7SL3 3.4 Å, Full-length insulin receptor bound with site 2 binding deficient mutant insulin (A-L13R)…
8DTM 3.5 Å, Cryo-EM structure of insulin receptor (IR) bound with S597 component 2
7SL2 3.6 Å, Full-length insulin receptor bound with site 2 binding deficient mutant insulin (A-L13R)…
7SL6 3.7 Å, Full-length insulin receptor bound with site 2 binding deficient mutant insulin (B-L17R)…
8EZ0 3.7 Å, Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically…
7STK 4.0 Å, Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound)…
7STJ 4.4 Å, Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound)…
8EYX 4.5 Å, Cryo-EM structure of 4 insulins bound full-length mouse IR mutant with physically…
7STI 4.9 Å, Full-length insulin receptor bound with unsaturated insulin WT (1 insulin bound)…

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