7SL4: Full-length insulin receptor

Full-length insulin receptor bound with site 2 binding deficient mutant insulin (B-L17R) -- asymmetric conformation. Determined by electron microscopy at 5.0 Å resolution. Released 30 Mar 2022.

Method: Electron microscopy
Resolution: 5.0 Å
Organisms: Mus musculus, Homo sapiens
Chains: 6
Atoms: 13,528
Mol. weight: 323.3 kDa
Released: 30 Mar 2022

Explore 7SL4 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7SL4 contains 50 α-helices and 144 β-strands across 6 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: 18 helices, 78 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	1
β-strand	9-13	5	2
α-helix	18-23	6
β-strand	26	1	1
β-strand	28-29	2	3
β-strand	30-38	9	2
α-helix	44-47	4
β-strand	56-57	2	3
β-strand	60-66	7	2
β-strand	71	1	4
β-strand	81-82	2	3
β-strand	93-98	6	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
β-strand	144-148	5	2
β-strand	171	1	5
β-strand	180	1	5
β-strand	182	1	6
β-strand	188	1	6
β-strand	201	1	7
β-strand	207	1	7
β-strand	213	1	8
β-strand	215	1	8
β-strand	216	1	9
β-strand	225	1	9
β-strand	231-233	3	10
β-strand	236-238	3	10
β-strand	246-248	3	10
β-strand	252-254	3	10
α-helix	256-267	12
β-strand	279	1	11
β-strand	283	1	10
β-strand	292-293	2	12
β-strand	300	1	11
β-strand	302-303	2	12
β-strand	311-312	2	13
β-strand	318-321	4	14
α-helix	325-327	3
β-strand	335-336	2	13
β-strand	339-342	4	14
α-helix	353-357	5
β-strand	363-364	2	13
β-strand	368-371	4	14
β-strand	378	1	15
β-strand	387-388	2	13
β-strand	394	1	14
β-strand	398-403	6	14
β-strand	410	1	15
β-strand	420-421	2	13
β-strand	425-429	5	14
β-strand	431	1	16
α-helix	436-446	11
β-strand	457	1	14
β-strand	462	1	16
β-strand	471-473	3	17
β-strand	475-479	5	18
β-strand	486-489	4	18
α-helix	497-499	3
β-strand	500-509	10	17
β-strand	531-534	4	17
α-helix	535-538	4
β-strand	553-554	2	18
β-strand	562-572	11	17
β-strand	583-585	3	17
β-strand	588-592	5	17
α-helix	598-600	3
β-strand	601-606	6	19
β-strand	613-618	6	19
β-strand	629-636	8	20
α-helix	638-640	3
α-helix	642-644	3
α-helix	695-715	21
β-strand	761-764	4	20
β-strand	769-772	4	19
β-strand	780-788	9	20
β-strand	797	1	20
α-helix	798-800	3
β-strand	801-806	6	20
α-helix	807-810	4
β-strand	815	1	21
β-strand	821-825	5	22
β-strand	829-833	5	22
β-strand	844-851	8	23
β-strand	859-864	6	23
α-helix	865-870	6
β-strand	874-877	4	22
α-helix	879-880	2
β-strand	883-884	2	24
β-strand	887-892	6	23
β-strand	895-896	2	23
β-strand	898	1	21
α-helix	899-902	4
β-strand	905-906	2	24

Chain B: 23 helices, 64 β-strands

Element	Residues	Length	Sheet
β-strand	9	1	25
β-strand	12-13	2	26
α-helix	17-23	7
β-strand	29	1	27
β-strand	30	1	25
β-strand	33-38	6	26
α-helix	43-45	3
β-strand	56-57	2	27
β-strand	61-66	6	26
β-strand	81-82	2	27
β-strand	93-98	6	26
β-strand	111-112	2	27
β-strand	117-122	6	26
α-helix	133-136	4
β-strand	144-148	5	26
α-helix	150-152	3
β-strand	171-173	3	28
β-strand	178-180	3	28
β-strand	201	1	29
β-strand	207	1	29
β-strand	213	1	30
β-strand	215	1	30
β-strand	216	1	31
α-helix	222-224	3
β-strand	225	1	31
β-strand	232	1	32
β-strand	246-248	3	32
β-strand	252-254	3	32
α-helix	256-267	12
β-strand	279	1	33
β-strand	283	1	32
β-strand	292-294	3	34
β-strand	300	1	33
β-strand	301-303	3	34
β-strand	311-321	11	35
α-helix	324-327	4
α-helix	328-330	3
β-strand	335-342	8	35
α-helix	351-357	7
β-strand	363-364	2	35
β-strand	368-371	4	35
β-strand	378	1	36
α-helix	379-381	3
β-strand	387-388	2	35
α-helix	393	1
β-strand	394	1	37
β-strand	398	1	37
β-strand	400-403	4	35
β-strand	410	1	36
β-strand	420-421	2	35
β-strand	428-429	2	35
α-helix	436-446	11
α-helix	449-451	3
β-strand	457	1	35
β-strand	472	1	38
β-strand	477-479	3	39
β-strand	485-488	4	39
α-helix	497-499	3
β-strand	502-509	8	38
β-strand	530-534	5	38
α-helix	535-538	4
β-strand	553-555	3	39
α-helix	558-559	2
β-strand	563-571	9	38
β-strand	584	1	38
β-strand	588-591	4	38
α-helix	592-594	3
β-strand	601-607	7	40
β-strand	613-618	6	40
α-helix	619-620	2
β-strand	629-636	8	41
α-helix	641-644	4
α-helix	707-715	9
β-strand	761-764	4	41
β-strand	769-772	4	40
β-strand	780-790	11	41
β-strand	796-797	2	41
β-strand	803-806	4	41
α-helix	807-810	4
β-strand	820-824	5	42
β-strand	830-834	5	42
β-strand	844-852	9	43
β-strand	858-864	7	43
α-helix	865-871	7
β-strand	874-876	3	42
β-strand	886-892	7	43
α-helix	898-902	5

Chain C: 1 helix, 1 β-strand

Element	Residues	Length	Sheet
α-helix	9-18	10
β-strand	24	1	44

Chain D: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	9-17	9

Chain E: 4 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	3	1
α-helix	4-8	5
α-helix	13-15	3
α-helix	17-19	3
β-strand	20	1	44

Chain F: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	2-3	2
α-helix	4-8	5
α-helix	13-18	6

Molecules and chains

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

Sequence of entity 1 (A, B), FASTA

>7SL4_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

>7SL4_2 Insulin B chain (chains C, D)
FVNQHLCGSHLVEALYRVCGERGFFYTPKT

Sequence of entity 3 (E, F), FASTA

>7SL4_3 Insulin A chain (chains E, F)
GIVEQCCTSICSLYQLENYCN

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)…
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…

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