8U4E: Insulin receptor

Cryo-EM structure of long form insulin receptor (IR-B) with three IGF2 bound, asymmetric conformation. Determined by electron microscopy at 4.2 Å resolution. Released 27 Mar 2024.

Method: Electron microscopy
Resolution: 4.2 Å
Organism: Homo sapiens
Chains: 5
Atoms: 13,948
Mol. weight: 373.55 kDa
Released: 27 Mar 2024

Explore 8U4E in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8U4E contains 49 α-helices and 154 β-strands across 5 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, 77 β-strands

Element	Residues	Length	Sheet
β-strand	9	1	1
β-strand	12-13	2	2
α-helix	19-25	7
β-strand	29	1	3
β-strand	30	1	1
β-strand	33-35	3	2
α-helix	43-46	4
β-strand	56-57	2	3
β-strand	61-66	6	2
β-strand	81-82	2	3
β-strand	91-98	8	2
β-strand	111-112	2	3
β-strand	116-122	7	2
α-helix	133-136	4
β-strand	137	1	3
β-strand	144-145	2	2
β-strand	148	1	2
β-strand	182	1	4
β-strand	188	1	4
β-strand	201	1	5
β-strand	207	1	5
β-strand	212-216	5	6
β-strand	225-228	4	6
β-strand	231-233	3	7
β-strand	236-238	3	7
β-strand	246-248	3	7
β-strand	252-254	3	7
α-helix	256-267	12
β-strand	278-280	3	7
β-strand	283-285	3	7
β-strand	292-294	3	8
β-strand	300	1	7
β-strand	301-303	3	8
β-strand	311-313	3	9
β-strand	318-321	4	10
α-helix	324-328	5
β-strand	335-337	3	9
β-strand	339-342	4	10
α-helix	352-357	6
β-strand	363-364	2	9
β-strand	368-371	4	10
β-strand	387-388	2	9
β-strand	394	1	11
β-strand	398	1	11
β-strand	400-403	4	10
β-strand	420-421	2	9
β-strand	426-429	4	10
β-strand	431	1	12
α-helix	436-446	11
β-strand	457	1	10
β-strand	462	1	12
β-strand	472-473	2	13
β-strand	475-477	3	14
β-strand	480	1	15
β-strand	485	1	15
β-strand	486-487	2	16
β-strand	488-489	2	14
α-helix	497-499	3
β-strand	500	1	17
β-strand	503-509	7	13
β-strand	530-534	5	13
α-helix	535-539	5
β-strand	551-552	2	16
β-strand	561-567	7	13
β-strand	570	1	17
β-strand	582-583	2	13
β-strand	586-589	4	13
α-helix	590-592	3
α-helix	597-598	2
β-strand	599-604	6	18
β-strand	611-616	6	18
β-strand	627-634	8	19
α-helix	635-638	4
α-helix	639-643	5
α-helix	693-713	21
β-strand	771-774	4	19
β-strand	779-782	4	18
β-strand	790-798	9	19
β-strand	807	1	19
β-strand	811-816	6	19
α-helix	817-820	4
β-strand	831	1	20
β-strand	834	1	21
β-strand	840-842	3	21
β-strand	843	1	20
β-strand	854-862	9	22
β-strand	868-874	7	22
α-helix	875-880	6
β-strand	884-886	3	21
α-helix	889-890	2
β-strand	893-894	2	23
β-strand	897-902	6	22
β-strand	906	1	22
α-helix	909-912	4
β-strand	915-916	2	23

Chain B: 23 helices, 75 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	24
β-strand	12-13	2	25
α-helix	17-23	7
β-strand	26	1	24
β-strand	28-29	2	26
β-strand	33-38	6	25
α-helix	43-48	6
β-strand	56-57	2	26
β-strand	61-66	6	25
β-strand	71	1	27
α-helix	72-74	3
β-strand	81-82	2	26
β-strand	93-96	4	25
β-strand	103	1	27
β-strand	111-112	2	26
β-strand	117-120	4	25
α-helix	140-142	3
β-strand	144-146	3	25
α-helix	149-152	4
β-strand	171-173	3	28
β-strand	178-180	3	28
β-strand	201	1	29
β-strand	207	1	29
β-strand	212	1	30
β-strand	216	1	31
α-helix	222-224	3
β-strand	225	1	31
β-strand	228	1	30
β-strand	232	1	32
β-strand	245-248	4	32
β-strand	252-255	4	32
α-helix	256-268	13
β-strand	278-279	2	33
β-strand	283	1	32
β-strand	284-285	2	33
β-strand	293-294	2	34
β-strand	300	1	33
β-strand	301-302	2	34
α-helix	303-304	2
β-strand	311-312	2	35
α-helix	313-314	2
α-helix	315-317	3
β-strand	318-321	4	36
α-helix	324-328	5
β-strand	335-336	2	35
β-strand	339-342	4	36
α-helix	351-357	7
β-strand	363-364	2	35
β-strand	368-371	4	36
β-strand	378	1	37
α-helix	379-381	3
β-strand	387-388	2	35
α-helix	393	1
β-strand	394	1	38
β-strand	398	1	38
β-strand	400-403	4	36
β-strand	410	1	37
β-strand	420-421	2	35
β-strand	425	1	38
β-strand	428	1	39
β-strand	431	1	40
α-helix	436-446	11
α-helix	449-451	3
β-strand	457	1	39
β-strand	462	1	40
β-strand	472-473	2	41
β-strand	477-479	3	42
β-strand	486-488	3	42
β-strand	503-509	7	41
β-strand	530-534	5	41
α-helix	535-537	3
β-strand	551-552	2	42
α-helix	556-557	2
β-strand	561-567	7	41
β-strand	582-583	2	41
β-strand	586-589	4	41
β-strand	599-604	6	43
β-strand	611-616	6	43
β-strand	627-634	8	44
α-helix	639-642	4
α-helix	701-714	14
β-strand	771-774	4	44
β-strand	779-782	4	43
β-strand	790-800	11	44
β-strand	806-807	2	44
β-strand	813-816	4	44
α-helix	817-819	3
β-strand	831-834	4	45
β-strand	840-843	4	45
β-strand	854-863	10	46
β-strand	868-874	7	46
α-helix	875-880	6
β-strand	884-886	3	45
β-strand	893	1	47
β-strand	894-902	9	46
β-strand	906	1	46
α-helix	908-912	5
β-strand	916	1	47

Chain C: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	14-21	8
α-helix	54-59	6

Chain D: 3 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	12-16	5
β-strand	26	1	48
α-helix	43-47	5
α-helix	54-57	4
β-strand	60	1	48

Chain E: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	12-21	10
α-helix	44-48	5
α-helix	54-58	5

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Insulin receptor	A, B	protein	1382	Homo sapiens	P06213 (AlphaFold model)
Insulin-like growth factor II	C, D, E	protein	180	Homo sapiens	P01344 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8U4E_1 Insulin receptor (chains A, B)
MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHL
QILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYAL
VIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNE
ECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECL
GNCSQPDDPTKCVACRNFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQG
CHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGC
TVINGSLIINIRGGNNLAAELEANLGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETL
EIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQE
RNDIALKTNGDQASCENELLKFSYIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQ
NVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFS
DERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVFWE
RQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQIL
KELEESSFRKTFEDYLHNVVFVPRKTSSGTGAEDPRPSRKRRSLGDVGNVTVAVPTVAAF
PNTSSTSVPTSPEEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYV
SARTMPEAKADDIVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCV
SRKHFALERGCRLRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIG
PLIFVFLFSVVIGSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSR
EKITLLRELGQGSFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKG
FTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMA
AEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPV
RWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDN
CPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEME
FEDMENVPLDRSSHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSN
PS

Sequence of entity 2 (C, D, E), FASTA

>8U4E_2 Insulin-like growth factor II (chains C, D, E)
MGIPMGKSMLVLLTFLAFASCCIAAYRPSETLCGGELVDTLQFVCGDRGFYFSRPASRVS
RRSRGIVEECCFRSCDLALLETYCATPAKSERDVSTPPTVLPDNFPRYPVGKFFQYDTWK
QSTQRLRRGLPALLRARRGHVLAKELEAFREAKRHRPLIALPTQDPAHGGAPPEMASNRK

Primary citation

Activation of the insulin receptor by insulin-like growth factor 2. An, W., Hall, C., Li, J. et al. Nat Commun (2024) 15:2609-2609. DOI 10.1038/s41467-024-46990-6 · PubMed

Other PDB entries of the same protein (UniProt P06213 (AlphaFold model), which also has an AlphaFold model), best resolution first:

3BU3 1.65 Å, Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide
5HHW 1.79 Å, Crystal structure of insulin receptor kinase domain in complex with…
4IBM 1.8 Å, Crystal structure of insulin receptor kinase domain in complex with an inhibitor Irfin-1
5U1M 1.8 Å, Structure of the IRS-1 PTB Domain Bound to the Juxtamembrane Region of the Insulin…
1IR3 1.9 Å, Phosphorylated insulin receptor tyrosine kinase in complex with peptide substrate and…
1P14 1.9 Å, Crystal structure of a catalytic-loop mutant of the insulin receptor tyrosine kinase
3BU6 1.95 Å, Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB phosphopeptide
1IRK 2.1 Å, Crystal structure of the tyrosine kinase domain of the human insulin receptor
3BU5 2.1 Å, Crystal structure of the insulin receptor kinase in complex with IRS2 KRLB peptide and ATP
3EKK 2.1 Å, Insulin receptor kinase complexed with an inhibitor
8DWN 2.15 Å, Crystal structure of bis-phosphorylated insulin receptor kinase domain
3EKN 2.2 Å, Insulin receptor kinase complexed with an inhibitor

Browse structure collections

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