8U4C: Insulin receptor

Cryo-EM structure of long form insulin receptor (IR-B) with four IGF2 bound, symmetric conformation. Determined by electron microscopy at 3.6 Å resolution. Released 27 Mar 2024.

Method: Electron microscopy
Resolution: 3.6 Å
Organism: Homo sapiens
Chains: 6
Atoms: 14,706
Mol. weight: 393.72 kDa
Released: 27 Mar 2024

Explore 8U4C in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8U4C contains 52 α-helices and 149 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: 21 helices, 74 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	1
β-strand	12-13	2	2
α-helix	17-23	7
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	117-120	4	2
α-helix	133-135	3
α-helix	140-142	3
β-strand	144-146	3	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	1	8
β-strand	216	1	9
α-helix	222-224	3
β-strand	225	1	9
β-strand	228	1	8
α-helix	241-242	2
β-strand	245-248	4	10
β-strand	252-255	4	10
α-helix	256-268	13
β-strand	278-279	2	11
β-strand	283	1	10
β-strand	284-285	2	11
β-strand	292-293	2	12
β-strand	300	1	11
β-strand	302-303	2	12
α-helix	304	1
β-strand	311-321	11	13
α-helix	324-328	5
β-strand	335-342	8	13
α-helix	351-357	7
β-strand	363-364	2	13
β-strand	368-370	3	13
β-strand	371	1	14
β-strand	378	1	15
β-strand	387-388	2	13
α-helix	393	1
β-strand	394	1	16
β-strand	398	1	16
β-strand	400	1	13
β-strand	403	1	14
β-strand	410	1	15
β-strand	420-421	2	13
β-strand	428	1	17
α-helix	436-446	11
β-strand	457	1	17
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	530-533	4	18
α-helix	535-538	4
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	597-598	2
β-strand	599-605	7	21
β-strand	611-616	6	21
β-strand	627-633	7	22
α-helix	636-638	3
α-helix	639-642	4
α-helix	693-713	21
β-strand	771-774	4	22
β-strand	779-782	4	21
β-strand	790-798	9	22
β-strand	807	1	22
β-strand	811-816	6	22
β-strand	827-834	8	23
β-strand	840-845	6	23
β-strand	854-863	10	24
β-strand	872	1	24
α-helix	875-880	6
β-strand	884-886	3	23
β-strand	892-902	11	24
β-strand	906	1	24
α-helix	907-911	5
β-strand	913-917	5	24

Chain B: 21 helices, 75 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	25
β-strand	12-13	2	26
α-helix	17-23	7
β-strand	26	1	25
β-strand	28-29	2	27
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	71	1	28
β-strand	81-82	2	27
β-strand	93-96	4	26
β-strand	103	1	28
β-strand	111-112	2	27
β-strand	117-120	4	26
α-helix	133-135	3
α-helix	140-142	3
β-strand	144-146	3	26
α-helix	149-152	4
β-strand	171-173	3	29
β-strand	178-180	3	29
β-strand	182	1	30
β-strand	188	1	30
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
α-helix	241-242	2
β-strand	245-248	4	34
β-strand	252-255	4	34
α-helix	256-268	13
β-strand	278-279	2	35
β-strand	283	1	34
β-strand	284-285	2	35
β-strand	292-293	2	36
β-strand	300	1	35
β-strand	302-303	2	36
α-helix	304	1
β-strand	311-321	11	37
α-helix	324-328	5
β-strand	335-342	8	37
α-helix	351-357	7
β-strand	363-364	2	37
β-strand	368-370	3	37
β-strand	371	1	38
β-strand	378	1	39
β-strand	387-388	2	37
α-helix	393	1
β-strand	394	1	40
β-strand	398	1	40
β-strand	400	1	37
β-strand	403	1	38
β-strand	410	1	39
β-strand	420-421	2	37
β-strand	428	1	41
α-helix	436-446	11
β-strand	457	1	41
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	530-533	4	42
α-helix	535-538	4
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	597-598	2
β-strand	599-605	7	45
β-strand	611-616	6	45
β-strand	627-633	7	46
α-helix	636-638	3
α-helix	639-642	4
α-helix	693-713	21
β-strand	771-774	4	46
β-strand	779-782	4	45
β-strand	790-798	9	46
β-strand	807	1	46
β-strand	811-816	6	46
β-strand	827-834	8	47
β-strand	840-845	6	47
β-strand	854-863	10	48
β-strand	868	1	48
β-strand	872	1	48
α-helix	875-880	6
β-strand	884-886	3	47
β-strand	892-902	11	48
β-strand	906	1	48
α-helix	907-911	5
β-strand	913-917	5	48

Chains C and E: 2 helices, 0 β-strands

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

Chains D and F: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	12-16	5
α-helix	43-47	5
α-helix	53-57	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, F	protein	180	Homo sapiens	P01344 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8U4C_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, F), FASTA

>8U4C_2 Insulin-like growth factor II (chains C, D, E, F)
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

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