7SL7: Full-length insulin receptor

Full-length insulin receptor bound with both site 1 binding deficient mutant insulin (A-V3E) and site 2 binding deficient mutant insulin (A-L13R). Determined by electron microscopy at 3.1 Å resolution. Released 30 Mar 2022.

Method: Electron microscopy
Resolution: 3.1 Å
Organisms: Mus musculus, Homo sapiens
Chains: 10
Atoms: 14,732
Mol. weight: 335 kDa
Released: 30 Mar 2022

Explore 7SL7 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7SL7 contains 63 α-helices and 153 β-strands across 10 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: 24 helices, 75 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	1
β-strand	11-14	4	2
α-helix	18-23	6
β-strand	26	1	1
β-strand	28-29	2	3
β-strand	33-38	6	2
α-helix	43-45	3
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	93-96	4	2
β-strand	103	1	4
β-strand	111-112	2	3
β-strand	117-122	6	2
α-helix	133-136	4
β-strand	137	1	3
α-helix	140-142	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	1	6
β-strand	188	1	6
β-strand	201	1	7
β-strand	207	1	7
β-strand	212-216	5	8
α-helix	222-224	3
β-strand	225-228	4	8
β-strand	231-233	3	9
β-strand	236-238	3	9
α-helix	241-242	2
β-strand	245-248	4	9
β-strand	252-255	4	9
α-helix	256-267	12
β-strand	278-279	2	10
β-strand	283	1	9
β-strand	284-285	2	10
β-strand	292-294	3	11
β-strand	300	1	10
β-strand	301-303	3	11
α-helix	304	1
β-strand	311-312	2	12
α-helix	315-317	3
β-strand	319-321	3	13
α-helix	324-328	5
β-strand	335-336	2	12
β-strand	340-342	3	13
α-helix	351-357	7
β-strand	363-364	2	12
β-strand	368-371	4	13
β-strand	378	1	14
β-strand	387-388	2	12
α-helix	393	1
β-strand	394	1	13
β-strand	398-403	6	13
β-strand	410	1	14
β-strand	420-421	2	12
β-strand	425-429	5	13
α-helix	436-446	11
α-helix	449-451	3
β-strand	457	1	13
β-strand	472-473	2	15
β-strand	475	1	16
β-strand	479-480	2	17
β-strand	485-487	3	17
β-strand	489	1	16
α-helix	497-499	3
β-strand	500-509	10	15
β-strand	530-534	5	15
β-strand	553-554	2	17
β-strand	563-572	10	15
β-strand	584-585	2	15
β-strand	588-591	4	15
α-helix	592-594	3
β-strand	601-606	6	18
β-strand	613-618	6	18
β-strand	629-636	8	19
α-helix	637-640	4
α-helix	641-645	5
α-helix	688-690	3
α-helix	691-715	25
β-strand	761-765	5	19
β-strand	769-772	4	18
β-strand	780-788	9	19
β-strand	801-806	6	19
α-helix	807-810	4
β-strand	821-824	4	20
β-strand	830-833	4	20
β-strand	844-853	10	21
β-strand	859-864	6	21
α-helix	865-871	7
β-strand	874-876	3	20
β-strand	882-883	2	22
β-strand	884-892	9	21
β-strand	896	1	21
α-helix	897-902	6
β-strand	903	1	21
β-strand	906-907	2	22

Chain B: 25 helices, 74 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	23
β-strand	11-14	4	24
α-helix	18-23	6
β-strand	26	1	23
β-strand	28-29	2	25
β-strand	33-38	6	24
α-helix	43-45	3
β-strand	56-57	2	25
β-strand	61-66	6	24
β-strand	71	1	26
β-strand	81-82	2	25
β-strand	93-96	4	24
β-strand	103	1	26
β-strand	111-112	2	25
β-strand	117-122	6	24
α-helix	133-136	4
β-strand	137	1	25
α-helix	140-142	3
β-strand	144-148	5	24
α-helix	149-152	4
β-strand	171-173	3	27
β-strand	178-180	3	27
β-strand	182	1	28
β-strand	188	1	28
α-helix	189-190	2
β-strand	201	1	29
β-strand	207	1	29
β-strand	212-216	5	30
α-helix	222-224	3
β-strand	225-228	4	30
β-strand	231-233	3	31
β-strand	236-238	3	31
α-helix	241-242	2
β-strand	245-248	4	31
β-strand	252-255	4	31
α-helix	256-267	12
β-strand	279	1	32
β-strand	283	1	31
β-strand	292-293	2	33
β-strand	300	1	32
β-strand	302-303	2	33
α-helix	304	1
β-strand	311-312	2	34
α-helix	315-317	3
β-strand	318-321	4	35
α-helix	324-328	5
β-strand	335-336	2	34
β-strand	339-342	4	35
α-helix	351-357	7
β-strand	363-364	2	34
β-strand	368-371	4	35
β-strand	378	1	36
β-strand	387-388	2	34
α-helix	393	1
β-strand	394	1	35
β-strand	398-403	6	35
β-strand	410	1	36
β-strand	420-421	2	34
β-strand	425-429	5	35
α-helix	436-446	11
α-helix	449-451	3
β-strand	457	1	35
β-strand	472-473	2	37
β-strand	475	1	38
β-strand	479-480	2	39
β-strand	485-487	3	39
β-strand	489	1	38
α-helix	497-499	3
β-strand	500-509	10	37
β-strand	530-534	5	37
β-strand	553-554	2	39
β-strand	563-572	10	37
β-strand	584-585	2	37
β-strand	588-591	4	37
α-helix	592-594	3
β-strand	601-606	6	40
β-strand	613-618	6	40
β-strand	629-636	8	41
α-helix	637-640	4
α-helix	641-645	5
α-helix	688-690	3
α-helix	691-715	25
β-strand	761-765	5	41
β-strand	769-772	4	40
β-strand	780-788	9	41
β-strand	801-806	6	41
α-helix	807-810	4
β-strand	821-824	4	42
β-strand	830-833	4	42
β-strand	844-853	10	43
β-strand	859-864	6	43
α-helix	865-871	7
β-strand	874-876	3	42
β-strand	882-883	2	44
β-strand	884-892	9	43
β-strand	896	1	43
α-helix	897-902	6
β-strand	903	1	43
β-strand	906-907	2	44

Chain C: 3 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	2-3	2
α-helix	4-8	5
α-helix	15-19	5
β-strand	20	1	45

Chain D: 3 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	2-3	2
α-helix	4-8	5
α-helix	13-17	5
β-strand	20	1	46

Chain E: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2-6	5
α-helix	14-17	4

Chain F: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2-6	5
α-helix	14-19	6

Chains G and H: 1 helix, 1 β-strand

Element	Residues	Length	Sheet
α-helix	9-18	10
β-strand	24	1	45

Chains I and J: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	9-18	10

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Insulin receptor	A, B	protein	1372	Mus musculus	P15208 (AlphaFold model)
Insulin B chain	G, H, I, J	protein	30	Homo sapiens	P01308 (AlphaFold model)
Insulin A chain (L13R)	C, D	protein	21	Homo sapiens	P01308 (AlphaFold model)
Insulin A chain (V3E)	E, F	protein	21	Homo sapiens	P01308 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7SL7_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 (G, H, I, J), FASTA

>7SL7_2 Insulin B chain (chains G, H, I, J)
FVNQHLCGSHLVEALYLVCGERGFFYTPKT

Sequence of entity 3 (C, D), FASTA

>7SL7_3 Insulin A chain (L13R) (chains C, D)
GIVEQCCTSICSRYQLENYCN

Sequence of entity 4 (E, F), FASTA

>7SL7_4 Insulin A chain (V3E) (chains E, F)
GIEEQCCTSICSLYQLENYCN

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
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)…
7STH 3.5 Å, Full-length insulin receptor bound with unsaturated insulin WT (2 insulin bound)…
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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