8VJC: Isoform Short of Insulin receptor

Cryo-EM structure of short form insulin receptor (IR-A) with three IGF2 bound, asymmetric conformation. Determined by electron microscopy at 3.8 Å resolution. Released 27 Mar 2024.

Method: Electron microscopy
Resolution: 3.8 Å
Organism: Homo sapiens
Chains: 5
Atoms: 13,927
Mol. weight: 371.17 kDa
Released: 27 Mar 2024

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

Secondary structure: helices and β-sheets

8VJC contains 48 α-helices and 147 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, 72 β-strands

Element	Residues	Length	Sheet
β-strand	9-13	5	1
α-helix	19-25	7
β-strand	28-29	2	2
β-strand	30-38	9	1
α-helix	43-45	3
β-strand	56-57	2	2
β-strand	61-66	6	1
β-strand	71	1	3
β-strand	81-82	2	2
β-strand	91-98	8	1
β-strand	103	1	3
β-strand	116-122	7	1
α-helix	133-136	4
β-strand	144-145	2	1
β-strand	148	1	1
β-strand	182	1	4
β-strand	188	1	4
β-strand	201	1	5
β-strand	207	1	5
β-strand	212	1	6
β-strand	213	1	7
β-strand	215	1	7
β-strand	216	1	8
β-strand	225	1	8
β-strand	228	1	6
β-strand	231-233	3	9
β-strand	236-238	3	9
β-strand	246-248	3	9
β-strand	252-254	3	9
α-helix	256-267	12
β-strand	278-280	3	9
β-strand	283-285	3	9
β-strand	292-294	3	10
β-strand	300	1	9
β-strand	301-303	3	10
α-helix	304	1
β-strand	311-313	3	11
β-strand	320-321	2	12
α-helix	324-328	5
β-strand	335-337	3	11
β-strand	340-342	3	12
α-helix	352-357	6
β-strand	363-364	2	11
β-strand	368-371	4	12
β-strand	378	1	13
β-strand	387-388	2	11
β-strand	394	1	12
β-strand	398-403	6	12
β-strand	410	1	13
β-strand	420-421	2	11
β-strand	425-429	5	12
α-helix	436-446	11
β-strand	457	1	12
β-strand	475-480	6	14
β-strand	485-489	5	14
β-strand	500-509	10	15
β-strand	530-534	5	15
α-helix	535-538	4
β-strand	551-552	2	14
β-strand	561-570	10	15
β-strand	582	1	15
β-strand	586-589	4	15
β-strand	599-605	7	16
β-strand	611-616	6	16
β-strand	627-634	8	17
α-helix	635-638	4
α-helix	639-643	5
α-helix	693-713	21
β-strand	759-762	4	17
β-strand	767-770	4	16
β-strand	778-786	9	17
β-strand	795	1	17
α-helix	796-798	3
β-strand	799-804	6	17
α-helix	805-808	4
β-strand	813	1	18
α-helix	817-818	2
β-strand	819-822	4	19
β-strand	828-831	4	19
β-strand	842-850	9	20
β-strand	856-862	7	20
α-helix	863-869	7
β-strand	872-874	3	19
α-helix	877-878	2
β-strand	881-882	2	21
β-strand	885-890	6	20
β-strand	894	1	20
β-strand	896	1	18
α-helix	897-899	3
β-strand	903-904	2	21

Chain B: 23 helices, 71 β-strands

Element	Residues	Length	Sheet
β-strand	6	1	22
β-strand	11-13	3	23
α-helix	17-23	7
β-strand	26	1	22
β-strand	28-29	2	24
β-strand	32-38	7	23
α-helix	43-46	4
β-strand	56-57	2	24
β-strand	60-66	7	23
β-strand	71	1	25
β-strand	81-82	2	24
β-strand	88	1	26
β-strand	91	1	26
β-strand	93-96	4	23
β-strand	103	1	25
β-strand	111-112	2	24
β-strand	117-120	4	23
α-helix	140-142	3
β-strand	144-146	3	23
α-helix	149-152	4
β-strand	171-173	3	27
β-strand	178-180	3	27
β-strand	201	1	28
β-strand	207	1	28
β-strand	212	1	29
β-strand	216	1	30
α-helix	222-224	3
β-strand	225	1	30
β-strand	228	1	29
β-strand	245-248	4	31
β-strand	252-255	4	31
α-helix	256-268	13
β-strand	278-279	2	32
β-strand	283	1	31
β-strand	284-285	2	32
β-strand	292-294	3	33
β-strand	300	1	32
β-strand	301-303	3	33
α-helix	304	1
β-strand	311-321	11	34
α-helix	324-327	4
α-helix	328-330	3
β-strand	335-342	8	34
α-helix	351-357	7
β-strand	363-366	4	34
β-strand	368-371	4	34
β-strand	378	1	35
β-strand	387-392	6	34
α-helix	393	1
β-strand	394	1	34
β-strand	398-403	6	34
β-strand	410	1	35
β-strand	420-421	2	34
β-strand	425-429	5	34
α-helix	436-445	10
α-helix	449-451	3
β-strand	457	1	34
β-strand	472	1	36
β-strand	475-479	5	37
β-strand	486-489	4	37
β-strand	502-509	8	36
β-strand	530-533	4	36
α-helix	535-538	4
β-strand	551-552	2	37
α-helix	556-557	2
β-strand	561-569	9	36
β-strand	582	1	36
α-helix	583-585	3
β-strand	586-589	4	36
α-helix	597-598	2
β-strand	599-604	6	38
β-strand	611-616	6	38
β-strand	627-634	8	39
α-helix	639-642	4
α-helix	702-714	13
β-strand	759-762	4	39
β-strand	767-770	4	38
β-strand	778-786	9	39
β-strand	788	1	40
β-strand	794	1	40
α-helix	797-798	2
β-strand	799-804	6	39
α-helix	805-807	3
β-strand	819-822	4	41
β-strand	828-831	4	41
β-strand	842-851	10	42
β-strand	856-862	7	42
α-helix	863-868	6
β-strand	872-874	3	41
β-strand	881	1	43
β-strand	882-890	9	42
β-strand	894	1	42
α-helix	896-900	5
β-strand	904	1	43

Chain C: 2 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	14-21	8
β-strand	26	1	44
α-helix	54-59	6
β-strand	60	1	44

Chain D: 3 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	12-16	5
β-strand	26	1	45
α-helix	43-47	5
α-helix	53-57	5
β-strand	60	1	45

Chain E: 2 helices, 0 β-strands

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

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Isoform Short of Insulin receptor	A, B	protein	1370	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

>8VJC_1 Isoform Short of Insulin receptor (chains A, B)
MATGGRRGAAAAPLLVAVAALLLGAAGHLYPGEVCPGMDIRNNLTRLHELENCSVIEGHL
QILLMFKTRPEDFRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGSRLFFNYAL
VIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYIVLNKDDNE
ECGDICPGTAKGKTNCPATVINGQFVERCWTHSHCQKVCPTICKSHGCTAEGLCCHSECL
GNCSQPDDPTKCVACRNFYLDGRCVETCPPPYYHFQDWRCVNFSFCQDLHHKCKNSRRQG
CHQYVIHNNKCIPECPSGYTMNSSNLLCTPCLGPCPKVCHLLEGEKTIDSVTSAQELRGC
TVINGSLIINIRGGNNLAAELEANLGLIEEISGYLKIRRSYALVSLSFFRKLRLIRGETL
EIGNYSFYALDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGRQE
RNDIALKTNGDQASCENELLKFSYIRTSFDKILLRWEPYWPPDFRDLLGFMLFYKEAPYQ
NVTEFDGQDACGSNSWTVVDIDPPLRSNDPKSQNHPGWLMRGLKPWTQYAIFVKTLVTFS
DERRTYGAKSDIIYVQTDATNPSVPLDPISVSNSSSQIILKWKPPSDPNGNITHYLVFWE
RQAEDSELFELDYCLKGLKLPSRTWSPPFESEDSQKHNQSEYEDSAGECCSCPKTDSQIL
KELEESSFRKTFEDYLHNVVFVPRPSRKRRSLGDVGNVTVAVPTVAAFPNTSSTSVPTSP
EEHRPFEKVVNKESLVISGLRHFTGYRIELQACNQDTPEERCSVAAYVSARTMPEAKADD
IVGPVTHEIFENNVVHLMWQEPKEPNGLIVLYEVSYRRYGDEELHLCVSRKHFALERGCR
LRGLSPGNYSVRIRATSLAGNGSWTEPTYFYVTDYLDVPSNIAKIIIGPLIFVFLFSVVI
GSIYLFLRKRQPDGPLGPLYASSNPEYLSASDVFPCSVYVPDEWEVSREKITLLRELGQG
SFGMVYEGNARDIIKGEAETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGV
VSKGQPTLVVMELMAHGDLKSYLRSLRPEAENNPGRPPPTLQEMIQMAAEIADGMAYLNA
KKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRWMAPESLKDGV
FTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMC
WQFNPKMRPTFLEIVNLLKDDLHPSFPEVSFFHSEENKAPESEELEMEFEDMENVPLDRS
SHCQREEAGGRDGGSSLGFKRSYEEHIPYTHMNGGKKNGRILTLPRSNPS

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

>8VJC_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

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