9Q2D: Ternary complex Ikaros-ZF2:CC-885:CRBN:DDB1

Cryo-EM structure of ternary complex Ikaros-ZF2:CC-885:CRBN:DDB1 (molecular glue degrader). Determined by electron microscopy at 2.94 Å resolution. Released 1 Oct 2025.

Method: Electron microscopy
Resolution: 2.94 Å
Organism: Homo sapiens
Chains: 3
Atoms: 9,352
Mol. weight: 157.23 kDa
Ligands: 85C, ZN
Released: 1 Oct 2025

Explore 9Q2D in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9Q2D contains 28 α-helices and 91 β-strands across 3 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: 1 helix, 2 β-strands

Element	Residues	Length	Sheet
β-strand	145-146	2	1
β-strand	153-154	2	1
α-helix	157-166	10

Chain B: 15 helices, 21 β-strands

Element	Residues	Length	Sheet
α-helix	53-56	4
α-helix	58-60	3
β-strand	65	1	2
β-strand	78-83	6	2
β-strand	96-101	6	2
α-helix	104-115	12
β-strand	119-123	5	2
β-strand	135-146	12	2
β-strand	155-172	18	2
β-strand	178-184	7	2
α-helix	200-205	6
α-helix	207-211	5
α-helix	219-231	13
α-helix	233-237	5
α-helix	242-245	4
α-helix	246-248	3
α-helix	250-262	13
α-helix	269-272	4
α-helix	277-285	9
α-helix	292-300	9
α-helix	304-317	14
β-strand	320-323	4	3
β-strand	330-333	4	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	4
β-strand	356-362	7	4
β-strand	368-371	4	4
β-strand	384	1	6
β-strand	387-391	5	4
β-strand	397-403	7	4
β-strand	404	1	6
β-strand	413-418	6	4
β-strand	422-425	4	3

Chain C: 12 helices, 68 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	130-134	5	11
β-strand	136	1	10
β-strand	139-144	6	11
β-strand	155-158	4	11
β-strand	163-169	7	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	210-211	2	12
β-strand	218-221	4	13
β-strand	229-232	4	13
β-strand	237-240	4	13
β-strand	245-248	4	13
α-helix	253-255	3
β-strand	258-263	6	14
β-strand	270-275	6	14
β-strand	279-288	10	14
β-strand	296-307	12	14
β-strand	313-318	6	15
β-strand	321-325	5	15
β-strand	332-336	5	15
β-strand	347-352	6	15
β-strand	361-365	5	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
α-helix	744	1
β-strand	749-751	3	17
β-strand	762-765	4	17
α-helix	766-768	3
β-strand	785-795	11	17
β-strand	801-806	6	17
β-strand	811-821	11	18
β-strand	824-835	12	18
β-strand	846-854	9	18
β-strand	857-866	10	18
β-strand	870-876	7	19
β-strand	879-884	6	19
β-strand	887-893	7	19
β-strand	899-906	8	19
β-strand	913-917	5	20
β-strand	920-924	5	20
β-strand	929-936	8	20
β-strand	941-949	9	20
β-strand	954-959	6	21
β-strand	964-969	6	21
β-strand	973-978	6	21
α-helix	986-989	4
β-strand	991	1	20
β-strand	993-999	7	21
β-strand	1004-1009	6	7
β-strand	1028-1032	5	7
β-strand	1037-1042	6	7
α-helix	1045-1058	14
α-helix	1070-1074	5
β-strand	1076-1077	2	22
β-strand	1082-1083	2	22
β-strand	1086	1	21
β-strand	1088-1090	3	7
α-helix	1091-1095	5
α-helix	1096-1098	3
α-helix	1102-1108	7
β-strand	1113-1114	2	23
β-strand	1122-1123	2	23
α-helix	1126-1137	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
DNA-binding protein Ikaros	A	protein	87	Homo sapiens	Q13422 (AlphaFold model)
Protein cereblon	B	protein	467	Homo sapiens	Q96SW2 (AlphaFold model)
DNA damage-binding protein 1	C	protein	836	Homo sapiens	Q16531 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>9Q2D_1 DNA-binding protein Ikaros (chains A)
GSLPNGKLKCDICGIICIGPNVLMVHKRSHTGERPFQCNQCGASFTQKGNLLRHIKLHSG
EKPFKCHLCNYACRRRDALTGHLRTHS

Sequence of entity 2 (B), FASTA

>9Q2D_2 Protein cereblon (chains B)
MSYYHHHHHHDYDIPTTGLVPRGSMMAGEGDQQDAAHNMGNHLPLLPAESEEEDEMEVED
QDSKEAKKPNIINFDTSLPTSHTYLGADMEEFHGRTLHDDDSCQVIPVLPQVMMILIPGQ
TLPLQLFHPQEVSMVRNLIQKDRTFAVLAYSNVQEREAQFGTTAEIYAYREEQDFGIEIV
KVKAIGRQRFKVLELRTQSDGIQQAKVQILPECVLPSTMSAVQLESLNKCQIFPSKPVSR
EDQCSYKWWQKYQKRKFHCANLTSWPRWLYSLYDAETLMDRIKKQLREWDENLKDDSLPS
NPIDFSYRVAACLPIDDVLRIQLLKIGSAIQRLRCELDIMNKCTSLCCKQCQETEITTKN
EIFSLSLCGPMAAYVNPHGYVHETLTVYKACNLNLIGRPSTEHSWFPGYAWTVAQCKICA
SHIGWKFTATKKDMSPQKFWGLTRSALLPTIPDTEDEISPDKVILCL

Sequence of entity 3 (C), FASTA

>9Q2D_3 DNA damage-binding protein 1 (chains C)
MSYNYVVTAQKPTAVNGCVTGHFTSAEDLNLLIAKNTRLEIYVVTAEGLRPVKEVGMYGK
IAVMELFRPKGESKDLLFILTAKYNACILEYKQSGESIDIITRAHGNVQDRIGRPSETGI
IGIIDPECRMIGLRLYDGLFKVIPLDRDNKELKAFNIRLEELHVIDVKFLYGCQAPTICF
VYQDPQGRHVKTYEVSLREKEFNKGPWKQENVEAEASMVIAVPEPFGGAIIIGQESITYH
NGDKYLAIAPPIIKQSTIVCHNRVDPNGSRYLLGDMEGRLFMLLLEKEEQMDGTVTLKDL
RVELLGETSIAECLTYLDNGVVFVGSRLGDSQLVKLNVDSNEQGSYVVAMETFTNLGPIV
DMCVVDLERQGQGQLVTCSGAFKEGSLRIIRNGIGGNGNSGEIQKLHIRTVPLYESPRKI
CYQEVSQCFGVLSSRIEVQDTSGGTTALRPSASTQALSSSVSSSKLFSSSTAPHETSFGE
EVEVHNLLIIDQHTFEVLHAHQFLQNEYALSLVSCKLGKDPNTYFIVGTAMVYPEEAEPK
QGRIVVFQYSDGKLQTVAEKEVKGAVYSMVEFNGKLLASINSTVRLYEWTTEKELRTECN
HYNNIMALYLKTKGDFILVGDLMRSVLLLAYKPMEGNFEEIARDFNPNWMSAVEILDDDN
FLGAENAFNLFVCQKDSAATTDEERQHLQEVGLFHLGEFVNVFCHGSLVMQNLGETSTPT
QGSVLFGTVNGMIGLVTSLSESWYNLLLDMQNRLNKVIKSVGKIEHSFWRSFHTERKTEP
ATGFIDGDLIESFLDISRPKMQEVVANLQYDDGSGMKREATADDLIKVVEELTRIH

Ligands and cofactors

ID	Name	Formula	Copies
85C	1-(3-chloro-4-methylphenyl)-3-({2-[(3S)-2,6-dioxopiperidin-3-yl]-1-oxo-2,3-dihy…	C22 H21 Cl N4 O4	1
ZN	Zinc ion	Zn	2

Primary citation

Application of Weighted Interaction-Fingerprints for Rationalizing Neosubstrate Potency and Selectivity of Cereblon-Based Molecular Glues. Luchini, G., Liu, S., Powers, H.L. et al. J Med Chem (2025) 68:20657-20674. DOI 10.1021/acs.jmedchem.5c01919 · PubMed

Other PDB entries of the same protein (UniProt Q13422 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8RQC 2.15 Å, Crystal structure of CRBN-midi in complex with mezigdomide and IKZF1 ZF2
8TNQ 2.41 Å, Cryo-EM structure of DDB1dB:CRBN:PT-179:SD40, conformation 1
8TNR 2.5 Å, Cryo-EM structure of DDB1dB:CRBN:PT-179:SD40, conformation 2
9OUK 2.69 Å, DDB1-CRBN with Ikaros(ZF2) and DEG-47: composite map and model submission
8D7Z 3.1 Å, Cereblon-DDB1 bound to CC-92480 and Ikaros ZF1-2-3
6H0F 3.25 Å, Structure of DDB1-CRBN-pomalidomide complex bound to IKZF1(ZF2)
9Y7D 3.26 Å, Cereblon with Golcadomide and Ikaros ZF1-2-3
8TNP 3.3 Å, Cryo-EM structure of DDB1dB:CRBN:Pomalidomide:SD40
8D80 3.6 Å, Cereblon~DDB1 bound to Iberdomide and Ikaros ZF1-2-3
9SQ5 3.68 Å, Cryo-EM structure of the DDB1deltaB-CRBN-Pomalidomide complex bound to…

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