8DEY: Ternary complex structure of Cereblon-DDB1

Ternary complex structure of Cereblon-DDB1 bound to IKZF2(ZF2,3) and the molecular glue DKY709. Determined by X-ray diffraction at 3.7 Å resolution. Released 8 Mar 2023.

Method: X-ray diffraction
Resolution: 3.7 Å
Organism: Homo sapiens
Chains: 6
Atoms: 19,332
Mol. weight: 286.53 kDa
Ligands: LWK, ZN
Released: 8 Mar 2023

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

Secondary structure: helices and β-sheets

8DEY contains 65 α-helices and 192 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: 15 helices, 21 β-strands

Element	Residues	Length	Sheet
α-helix	73-74	2
β-strand	78-83	6	1
β-strand	96-101	6	1
α-helix	104-113	10
β-strand	119-127	9	1
β-strand	132-144	13	1
β-strand	147	1	2
α-helix	149-151	3
β-strand	154	1	2
β-strand	155-172	18	1
β-strand	178-184	7	1
α-helix	185-187	3
α-helix	200-205	6
α-helix	222-231	10
α-helix	233-237	5
α-helix	242-246	5
α-helix	250-257	8
α-helix	269-272	4
α-helix	277-285	9
α-helix	292-299	8
α-helix	304-317	14
β-strand	321-323	3	3
β-strand	330-332	3	3
α-helix	334-336	3
β-strand	337	1	4
β-strand	341	1	5
β-strand	344	1	5
β-strand	346-350	5	6
β-strand	356-360	5	6
β-strand	362	1	4
β-strand	368-375	8	6
β-strand	384-391	8	6
β-strand	397-404	8	6
β-strand	417-418	2	6
α-helix	419-421	3
β-strand	422-423	2	3

Chain B: 15 helices, 70 β-strands

Element	Residues	Length	Sheet
β-strand	4-10	7	7
β-strand	17-21	5	8
β-strand	30-35	6	8
β-strand	38-44	7	8
β-strand	49-56	8	8
β-strand	61-67	7	9
β-strand	76-81	6	9
β-strand	85-94	10	9
β-strand	97-107	11	9
β-strand	115	1	10
β-strand	121-124	4	11
β-strand	131-134	4	11
β-strand	136	1	10
β-strand	139-143	5	11
β-strand	155-158	4	11
β-strand	164-169	6	12
α-helix	170	1
β-strand	177-184	8	12
β-strand	187-196	10	12
β-strand	201-204	4	12
β-strand	209	1	12
β-strand	218-221	4	13
β-strand	229-232	4	13
β-strand	237-241	5	13
β-strand	244-248	5	13
α-helix	251-253	3
β-strand	258-263	6	14
β-strand	270-275	6	14
β-strand	279-286	8	14
β-strand	299-307	9	14
α-helix	310	1
β-strand	311-316	6	15
β-strand	321-326	6	15
β-strand	331-336	6	15
β-strand	347-353	7	15
β-strand	359-365	7	16
β-strand	374-379	6	16
α-helix	382-384	3
β-strand	386-392	7	16
β-strand	710-716	7	16
β-strand	720-727	8	17
β-strand	732-743	12	17
β-strand	749-751	3	17
α-helix	756-758	3
β-strand	763-765	3	17
α-helix	769-772	4
β-strand	785-795	11	17
β-strand	801-806	6	17
α-helix	807-808	2
β-strand	811-820	10	18
β-strand	827-835	9	18
β-strand	837	1	19
β-strand	840	1	19
β-strand	846-854	9	18
β-strand	857-866	10	18
β-strand	870-876	7	20
β-strand	879-884	6	20
β-strand	887-893	7	20
β-strand	899-906	8	20
β-strand	913-917	5	21
β-strand	920-924	5	21
β-strand	930-936	7	21
β-strand	941-948	8	21
β-strand	956-959	4	22
β-strand	964-968	5	22
β-strand	973-978	6	22
β-strand	991	1	21
β-strand	996-999	4	22
β-strand	1004-1009	6	7
β-strand	1025-1032	8	7
β-strand	1037-1042	6	7
α-helix	1045-1061	17
α-helix	1065-1067	3
α-helix	1070-1073	4
β-strand	1076-1077	2	23
β-strand	1082-1083	2	23
β-strand	1086	1	22
β-strand	1088-1090	3	7
α-helix	1091-1095	5
α-helix	1096-1099	4
α-helix	1102-1109	8
β-strand	1113-1115	3	24
β-strand	1121-1123	3	24
α-helix	1124-1125	2
α-helix	1126-1137	12

Chains C and F: 2 helices, 4 β-strands

Element	Residues	Length	Sheet
β-strand	140-141	2	25
β-strand	148-149	2	25
α-helix	152-163	12
β-strand	168-169	2	26
β-strand	176-177	2	26
α-helix	180-191	12

Chain D: 16 helices, 23 β-strands

Element	Residues	Length	Sheet
α-helix	73-74	2
β-strand	78-83	6	27
β-strand	93	1	27
β-strand	96-100	5	27
α-helix	104-113	10
β-strand	119	1	27
β-strand	121-127	7	27
β-strand	132-144	13	27
α-helix	149-151	3
β-strand	156-172	17	27
β-strand	178-184	7	27
α-helix	185-187	3
β-strand	188	1	28
α-helix	200-202	3
α-helix	203-206	4
α-helix	222-230	9
α-helix	233-237	5
α-helix	242-246	5
α-helix	250-257	8
α-helix	269-272	4
α-helix	277-285	9
α-helix	292-297	6
β-strand	303	1	28
α-helix	304-317	14
β-strand	321-323	3	29
β-strand	330-332	3	29
α-helix	334-336	3
β-strand	337	1	30
β-strand	341	1	31
β-strand	344	1	31
β-strand	346-350	5	30
β-strand	356-362	7	30
β-strand	368-369	2	30
β-strand	375	1	30
β-strand	384-391	8	30
β-strand	397-404	8	30
β-strand	413-418	6	30
α-helix	419-421	3
β-strand	422-423	2	29

Chain E: 15 helices, 70 β-strands

Element	Residues	Length	Sheet
β-strand	4-10	7	32
β-strand	17-21	5	33
β-strand	30-35	6	33
β-strand	38-44	7	33
β-strand	49-56	8	33
β-strand	61-67	7	34
β-strand	76-81	6	34
β-strand	85-94	10	34
β-strand	97-107	11	34
β-strand	115	1	35
β-strand	121-124	4	36
β-strand	131-134	4	36
β-strand	136	1	35
β-strand	139-143	5	36
β-strand	155-158	4	36
β-strand	164-169	6	37
α-helix	170	1
β-strand	177-184	8	37
β-strand	187-196	10	37
β-strand	201-204	4	37
β-strand	209	1	37
β-strand	218-221	4	38
β-strand	229-232	4	38
β-strand	237-241	5	38
β-strand	244-248	5	38
α-helix	251-253	3
β-strand	258-263	6	39
β-strand	270-275	6	39
β-strand	279-286	8	39
β-strand	299-307	9	39
α-helix	310-311	2
β-strand	313-318	6	40
β-strand	321-325	5	40
β-strand	331-336	6	40
β-strand	347-353	7	40
β-strand	359-365	7	41
β-strand	374-379	6	41
α-helix	382-384	3
β-strand	386-392	7	41
β-strand	710-716	7	41
β-strand	720-727	8	42
β-strand	732-743	12	42
β-strand	749-751	3	42
α-helix	756-758	3
β-strand	763-765	3	42
α-helix	769-772	4
β-strand	785-795	11	42
β-strand	801-806	6	42
α-helix	807-808	2
β-strand	811-821	11	43
β-strand	824-835	12	43
β-strand	837	1	44
β-strand	840	1	44
β-strand	846-854	9	43
β-strand	857-866	10	43
β-strand	870-876	7	45
β-strand	879-884	6	45
β-strand	887-893	7	45
β-strand	899-906	8	45
β-strand	913-917	5	46
β-strand	920-924	5	46
β-strand	930-936	7	46
β-strand	941-948	8	46
β-strand	954-959	6	47
β-strand	964-969	6	47
β-strand	973-978	6	47
β-strand	991	1	46
β-strand	996-999	4	47
β-strand	1004-1008	5	32
β-strand	1025-1032	8	32
β-strand	1037-1042	6	32
α-helix	1045-1058	14
α-helix	1065-1067	3
α-helix	1070-1073	4
β-strand	1076-1077	2	48
β-strand	1082-1083	2	48
β-strand	1086	1	47
β-strand	1088-1090	3	32
α-helix	1091-1095	5
α-helix	1096-1099	4
α-helix	1102-1109	8
β-strand	1113-1115	3	49
β-strand	1121-1123	3	49
α-helix	1124-1125	2
α-helix	1126-1137	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Protein cereblon	A, D	protein	373	Homo sapiens	Q96SW2 (AlphaFold model)
DNA damage-binding protein 1	B, E	protein	836	Homo sapiens	Q16531 (AlphaFold model)
Zinc finger protein Helios	C, F	protein	57	Homo sapiens	Q9UKS7 (AlphaFold model)

Sequence of entity 1 (A, D), FASTA

>8DEY_1 Protein cereblon (chains A, D)
RTLHDDDSCQVIPVLPQVMMILIPGQTLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQ
EREAQFGTTAEIYAYREEQDFGIEIVKVKAIGRQRFKVLELRTQSDGIQQAKVQILPECV
LPSTMSAVQLESLNKCQIFPSKPVSREDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYD
AETLMDRIKKQLREWDENLKDDSLPSNPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLR
CELDIMNKCTSLCCKQCQETEITTKNEIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLN
LIGRPSTEHSWFPGYAWTVAQCKICASHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDT
EDEISPDKVILCL

Sequence of entity 2 (B, E), FASTA

>8DEY_2 DNA damage-binding protein 1 (chains B, E)
MSYNYVVTAQKPTAVNGCVTGHFTSAEDLNLLIAKNTRLEIYVVTAEGLRPVKEVGMYGK
IAVMELFRPKGESKDLLFILTAKYNACILEYKQSGESIDIITRAHGNVQDRIGRPSETGI
IGIIDPECRMIGLRLYDGLFKVIPLDRDNKELKAFNIRLEELHVIDVKFLYGCQAPTICF
VYQDPQGRHVKTYEVSLREKEFNKGPWKQENVEAEASMVIAVPEPFGGAIIIGQESITYH
NGDKYLAIAPPIIKQSTIVCHNRVDPNGSRYLLGDMEGRLFMLLLEKEEQMDGTVTLKDL
RVELLGETSIAECLTYLDNGVVFVGSRLGDSQLVKLNVDSNEQGSYVVAMETFTNLGPIV
DMCVVDLERQGQGQLVTCSGAFKEGSLRIIRNGIGGNGNSGEIQKLHIRTVPLYESPRKI
CYQEVSQCFGVLSSRIEVQDTSGGTTALRPSASTQALSSSVSSSKLFSSSTAPHETSFGE
EVEVHNLLIIDQHTFEVLHAHQFLQNEYALSLVSCKLGKDPNTYFIVGTAMVYPEEAEPK
QGRIVVFQYSDGKLQTVAEKEVKGAVYSMVEFNGKLLASINSTVRLYEWTTEKELRTECN
HYNNIMALYLKTKGDFILVGDLMRSVLLLAYKPMEGNFEEIARDFNPNWMSAVEILDDDN
FLGAENAFNLFVCQKDSAATTDEERQHLQEVGLFHLGEFVNVFCHGSLVMQNLGETSTPT
QGSVLFGTVNGMIGLVTSLSESWYNLLLDMQNRLNKVIKSVGKIEHSFWRSFHTERKTEP
ATGFIDGDLIESFLDISRPKMQEVVANLQYDDGSGMKREATADDLIKVVEELTRIH

Sequence of entity 3 (C, F), FASTA

>8DEY_3 Zinc finger protein Helios (chains C, F)
SERPFHCNQCGASFTQKGNLLRHIKLHSGEKPFKCPFCSYACRRRDALTGHLRTHSV

Ligands and cofactors

ID	Name	Formula	Copies
LWK	(3S)-3-[5-(1-benzylpiperidin-4-yl)-1-oxo-1,3-dihydro-2H-isoindol-2-yl]piperidin…	C25 H27 N3 O3	1
ZN	Zinc ion	Zn	6

Primary citation

Discovery and characterization of a selective IKZF2 glue degrader for cancer immunotherapy. Bonazzi, S., d'Hennezel, E., Beckwith, R.E.J. et al. Cell Chem Biol (2023) 30:235-247.e12. DOI 10.1016/j.chembiol.2023.02.005 · PubMed

Other PDB entries of the same protein (UniProt Q96SW2 (AlphaFold model), which also has an AlphaFold model), best resolution first:

4M91 1.1 Å, crystal structure of hN33/Tusc3-peptide 1
9CUO 1.6 Å, Crystal structure of CRBN with compound 3
9OHQ 1.6 Å, Structure of CRBN:IKZF2:Compound 15
9DOM 1.69 Å, PVTX-405: A Potent, Highly Selective, and Orally Efficacious Molecular Glue Degrader of…
7BQV 1.8 Å, Cereblon in complex with SALL4 and (S)-5-hydroxythalidomide
9O91 1.86 Å, Structure of IKZF2:CRBN:Compound 5 ternary structure
7BQU 1.9 Å, Cereblon in complex with SALL4 and (S)-thalidomide
9GAO 1.95 Å, Crystal structure of CRBNmidi in complex with 2-(4-(2,6-dioxopiperidin-3-yl)phenoxy)-N-me…
9FJX 2.0 Å, Crystal structure of human CRBN-DDB1 in complex with Lenalidomide
8RQC 2.15 Å, Crystal structure of CRBN-midi in complex with mezigdomide and IKZF1 ZF2
8RQ8 2.19 Å, Crystal structure of CRBN-midi in complex with mezigdomide
9OHR 2.34 Å, Structure of CRBN:IKZF2:Compound 35

Browse structure collections

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