9I2C: PDB entry 9I2C

Name: PDB 9I2C: Cryo-EM structure of KBTBD4 WT-HDAC2-CoREST1 2:1:1 complex mediated by molecular glue UM171
Published: 2025-04-09
License: https://creativecommons.org/publicdomain/zero/1.0/
Keywords: ligase

Cryo-EM structure of KBTBD4 WT-HDAC2-CoREST1 2:1:1 complex mediated by molecular glue UM171. Determined by electron microscopy at 3.3 Å resolution. Released 9 Apr 2025.

Method: Electron microscopy
Resolution: 3.3 Å
Organism: Homo sapiens
Chains: 4
Atoms: 9,912
Mol. weight: 194.61 kDa
Ligands: A1ACV, ZN
Released: 9 Apr 2025

Explore 9I2C in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9I2C contains 52 α-helices and 86 β-strands across 4 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: 17 helices, 39 β-strands

Element	Residues	Length	Sheet
β-strand	14	1	1
β-strand	18-22	5	1
α-helix	26-34	9
α-helix	35-39	5
β-strand	47-51	5	2
β-strand	55-58	4	2
α-helix	60-66	7
α-helix	68-75	8
β-strand	85-88	4	2
α-helix	93-105	13
β-strand	107-111	5	3
α-helix	115-124	10
α-helix	128-140	13
α-helix	147-157	11
α-helix	160-177	18
α-helix	188-196	9
α-helix	201-203	3
α-helix	205-213	9
α-helix	226-229	4
β-strand	240-244	5	4
β-strand	253-260	8	4
β-strand	264-271	8	4
β-strand	277-283	7	5
β-strand	286-291	6	5
β-strand	299-301	3	5
α-helix	308	1
β-strand	309-310	2	5
α-helix	312-314	3
β-strand	319	1	6
β-strand	322-326	5	7
β-strand	331-335	5	7
β-strand	338	1	6
β-strand	344	1	6
β-strand	348-352	5	7
β-strand	358-360	3	7
α-helix	362-364	3
β-strand	372-376	5	8
β-strand	379-388	10	8
β-strand	394-404	11	8
β-strand	409-416	8	8
β-strand	423-428	6	9
β-strand	431-436	6	9
β-strand	437	1	10
β-strand	440-442	3	9
β-strand	445	1	11
β-strand	450	1	11
β-strand	454-455	2	9
β-strand	466	1	10
β-strand	468-472	5	12
β-strand	475-479	5	12
β-strand	482	1	13
β-strand	490-494	5	12
α-helix	496-498	3
β-strand	499-503	5	12
β-strand	512	1	13
β-strand	513-517	5	4

Chain B: 16 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	16-19	4	14
α-helix	22-24	3
α-helix	38-50	13
β-strand	57-60	4	14
α-helix	61-65	5
α-helix	66-69	4
α-helix	75-83	9
α-helix	87-89	3
α-helix	111-127	17
β-strand	136-139	4	14
α-helix	160-168	9
β-strand	175-179	5	14
α-helix	186-191	6
β-strand	198-203	6	14
α-helix	222-224	3
β-strand	229-231	3	14
α-helix	239-257	19
β-strand	261-265	5	14
α-helix	283-286	4
α-helix	289-294	6
β-strand	300-303	4	14
α-helix	310-324	15
β-strand	332	1	15
β-strand	347	1	15
α-helix	351-353	3
α-helix	361-376	16

Chain C: 15 helices, 36 β-strands

Element	Residues	Length	Sheet
β-strand	18-22	5	3
α-helix	26-35	10
α-helix	36-40	5
β-strand	48-51	4	16
β-strand	54-56	3	16
α-helix	60-63	4
α-helix	68-75	8
β-strand	85-87	3	16
α-helix	93-104	12
β-strand	107-111	5	1
α-helix	116-124	9
α-helix	128-141	14
α-helix	147-156	10
α-helix	160-172	13
α-helix	188-196	9
α-helix	201-203	3
α-helix	205-211	7
α-helix	225-229	5
β-strand	241-244	4	17
β-strand	253-254	2	17
β-strand	258	1	18
β-strand	266	1	18
β-strand	271-272	2	17
β-strand	280-283	4	19
β-strand	286-289	4	19
β-strand	299	1	19
α-helix	312-314	3
β-strand	318-319	2	20
β-strand	322-324	3	21
β-strand	331	1	22
β-strand	333-335	3	21
β-strand	338-339	2	20
β-strand	344	1	20
β-strand	349	1	21
β-strand	352	1	22
β-strand	360	1	21
α-helix	362-364	3
β-strand	369	1	23
β-strand	372-376	5	23
β-strand	379-389	11	23
β-strand	393-404	12	23
β-strand	409-413	5	23
β-strand	424-427	4	24
β-strand	432-435	4	24
β-strand	440-444	5	24
β-strand	451-455	5	24
β-strand	467-469	3	25
β-strand	476-480	5	25
β-strand	491-494	4	25
β-strand	499-502	4	25
β-strand	513-517	5	17

Chain D: 4 helices, 1 β-strand

Element	Residues	Length	Sheet
β-strand	135-138	4	14
α-helix	146-159	14
α-helix	164-173	10
α-helix	178-184	7
α-helix	232-240	9

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Isoform 1 of Kelch repeat and BTB domain-containing protein 4	A, C	protein	518	Homo sapiens	Q9NVX7 (AlphaFold model)
Histone deacetylase 2	B	protein	488	Homo sapiens	Q92769 (AlphaFold model)
REST corepressor 1	D	protein	190	Homo sapiens	Q9UKL0 (AlphaFold model)

Sequence of entity 1 (A, C), FASTA

>9I2C_1 Isoform 1 of Kelch repeat and BTB domain-containing protein 4 (chains A, C)
MESPEEPGASMDENYFVNYTFKDRSHSGRVAQGIMKLCLEEELFADVTISVEGREFQLHR
LVLSAQSCFFRSMFTSNLKEAHNRVIVLQDVSESVFQLLVDYIYHGTVKLRAEELQEIYE
VSDMYQLTSLFEECSRFLARTVQVGNCLQVMWLADRHSDPELYTAAKHCAKTHLAQLQNT
EEFLHLPHRLLTDIISDGVPCSQNPTEAIEAWINFNKEEREAFAESLRTSLKEIGENVHI
YLIGKESSRTHSLAVSLHCAEDDSISVSGQNSLCHQITAACKHGGDLYVVGGSIPRRMWK
CNNATVDWEWCAPLPRDRLQHTLVSVPGKDAIYSLGGKTLQDTLSNAVIYYRVGDNVWTE
TTQLEVAVSGAAGANLNGIIYLLGGEENDLDFFTKPSRLIQCFDTETDKCHVKPYVLPFA
GRMHAAVHKDLVFIVAEGDSLVCYNPLLDSFTRLCLPEAWSSAPSLWKIASCNGSIYVFR
DRYKKGDANTYKLDPATSAVTVTRGIKVLLTNLQFVLA

Sequence of entity 2 (B), FASTA

>9I2C_2 Histone deacetylase 2 (chains B)
MAYSQGGGKKKVCYYYDGDIGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKA
TAEEMTKYHSDEYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVA
GAVKLNRQQTDMAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHH
GDGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNFPMRDGIDDESYGQ
IFKPIISKVMEMYQPSAVVLQCGADSLSGDRLGCFNLTVKGHAKCVEVVKTFNLPLLMLG
GGGYTIRNVARCWTYETAVALDCEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTPEYM
EKIKQRLFENLRMLPHAPGVQMQAIPEDAVHEDSGDEDGEDPDKRISIRASDKRIACDEE
FSDSEDEGEGGRRNVADHKKGAKKARIEEDKKETEDKKTDVKEEDKSKDNSGEKTDTKGT
KSEQLSNP

Sequence of entity 3 (D), FASTA

>9I2C_3 REST corepressor 1 (chains D)
MSWEEGSSGSSSDEEHGGGGMRVGPQYQAVVPDFDPAKLARRSQERDNLGMLVWSPNQNL
SEAKLDEYIAIAKEKHGYNMEQALGMLFWHKHNIEKSLADLPNFTPFPDEWTVEDKVLFE
QAFSFHGKTFHRIQQMLPDKSIASLVKFYYSWKKTRTKTSVMDRAENLYFQSHHHHHHHH
HHDYKDDDDK

Ligands and cofactors

ID	Name	Formula	Copies
A1ACV	(1r,4r)-N~1~-[(7P)-2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]ind…	C25 H27 N9	1
ZN	Zinc ion	Zn	1

Primary citation

Structural mimicry of UM171 and neomorphic cancer mutants co-opts E3 ligase KBTBD4 for HDAC1/2 recruitment. Chen, Z., Chi, G., Balo, T. et al. Nat Commun (2025) 16:3144-3144. DOI 10.1038/s41467-025-58350-z · PubMed

Other PDB entries of the same protein (UniProt Q9NVX7 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9GGM 2.71 Å, Cryo-EM structure of KBTBD4 P313PRR mutant-HDAC2 2:2 complex
9DTQ 2.87 Å, The structure of HDAC2-CoREST in complex with KBTBD4R313PRR mutant
9GGN 2.9 Å, Cryo-EM structure of KBTBD4 WT-HDAC2 2:2 complex mediated by molecular glue UM171
9GGL 3.13 Å, Cryo-EM structure of KBTBD4 WT-HDAC2 2:1 complex mediated by molecular glue UM171
8VPQ 3.3 Å, The structure of LSD1-CoREST-HDAC1 in complex with KBTBD4IPR310delinsTTYML
8VRT 3.42 Å, The structure of LSD1-CoREST-HDAC1 in complex with KBTBD4R313PRR mutant
8VOJ 3.77 Å, The Cryo-EM structure of LSD1-CoREST-HDAC1 in complex with KBTBD4 enhanced by UM171 and…
9DTG 3.83 Å, The cryo-EM structure of apo KBTBD4
2EQX Solution structure of the BACK domain of Kelch repeat and BTB domain-containing protein 4

Browse structure collections

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