8VOJ: LSD1-CoREST-HDAC1

The Cryo-EM structure of LSD1-CoREST-HDAC1 in complex with KBTBD4 enhanced by UM171 and IP6. Determined by electron microscopy at 3.77 Å resolution. Released 4 Dec 2024.

Method: Electron microscopy
Resolution: 3.77 Å
Organism: Homo sapiens
Chains: 4
Atoms: 12,109
Mol. weight: 222.28 kDa
Ligands: A1ACV, IHP, ZN
Released: 4 Dec 2024

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

Secondary structure: helices and β-sheets

8VOJ contains 53 α-helices and 108 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: 14 helices, 47 β-strands

Element	Residues	Length	Sheet
β-strand	26	1	1
β-strand	30	1	2
β-strand	34-38	5	2
α-helix	44-53	10
β-strand	63-67	5	3
β-strand	70-74	5	3
α-helix	76-82	7
α-helix	84-90	7
β-strand	101-103	3	3
α-helix	110-120	11
β-strand	123-127	5	4
α-helix	132-140	9
α-helix	144-155	12
α-helix	163-166	4
α-helix	168-171	4
α-helix	176-187	12
α-helix	197-200	4
α-helix	204-211	8
β-strand	215-216	2	5
α-helix	221-229	9
α-helix	233-244	12
β-strand	249-250	2	5
β-strand	255-259	5	6
β-strand	260	1	7
β-strand	268	1	8
β-strand	269	1	7
β-strand	272-274	3	6
β-strand	282-283	2	6
β-strand	289	1	8
β-strand	293-299	7	9
β-strand	302-307	6	9
β-strand	313-318	6	9
β-strand	323-326	4	9
α-helix	328-330	3
β-strand	335	1	10
β-strand	338-342	5	11
β-strand	347-351	5	11
β-strand	354	1	10
β-strand	360	1	10
β-strand	365-368	4	11
β-strand	373-376	4	11
β-strand	384-385	2	12
β-strand	388-391	4	13
β-strand	395-399	5	13
β-strand	401	1	14
β-strand	402-404	3	12
β-strand	410-412	3	12
β-strand	416-420	5	13
β-strand	426-428	3	13
β-strand	437	1	14
β-strand	439-444	6	15
β-strand	447-452	6	15
β-strand	457-460	4	15
β-strand	461	1	16
β-strand	466	1	16
β-strand	469-470	2	15
β-strand	484-488	5	17
β-strand	491-495	5	17
β-strand	506-510	5	17
β-strand	515-518	4	17
β-strand	531-533	3	6

Chain B: 17 helices, 46 β-strands

Element	Residues	Length	Sheet
β-strand	30	1	4
β-strand	34-38	5	4
α-helix	44-53	10
β-strand	63-67	5	18
β-strand	70-74	5	18
α-helix	76-82	7
α-helix	84-90	7
β-strand	101-103	3	18
α-helix	110-120	11
β-strand	123-127	5	2
α-helix	128-130	3
α-helix	132-140	9
α-helix	144-156	13
α-helix	167-171	5
α-helix	176-187	12
α-helix	190-193	4
α-helix	197-200	4
α-helix	204-211	8
β-strand	215-216	2	19
α-helix	217-219	3
α-helix	221-229	9
α-helix	233-244	12
β-strand	249-250	2	19
β-strand	255-259	5	20
β-strand	260-261	2	21
β-strand	268-269	2	21
β-strand	272-274	3	20
β-strand	282-283	2	20
β-strand	289	1	21
β-strand	293-299	7	22
β-strand	302-307	6	22
β-strand	313-317	5	22
β-strand	324-326	3	22
α-helix	328-330	3
β-strand	335	1	23
β-strand	338-342	5	24
β-strand	347-351	5	24
β-strand	354	1	23
β-strand	360	1	23
β-strand	365-368	4	24
β-strand	374-376	3	24
α-helix	378-380	3
β-strand	384-385	2	25
β-strand	388-391	4	26
β-strand	395-399	5	26
β-strand	401	1	27
β-strand	402-404	3	25
β-strand	410-412	3	25
β-strand	416-420	5	26
β-strand	426-428	3	26
β-strand	437	1	27
β-strand	439-444	6	28
β-strand	447-452	6	28
β-strand	457-460	4	28
β-strand	461	1	29
β-strand	466	1	29
β-strand	468	1	1
β-strand	469-470	2	28
β-strand	484-488	5	30
β-strand	491-495	5	30
β-strand	506-510	5	30
β-strand	515-518	4	30
β-strand	531-533	3	20

Chain C: 14 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	11-14	4	31
α-helix	34-45	12
α-helix	47-50	4
β-strand	52-56	5	31
α-helix	57-58	2
α-helix	70-78	9
α-helix	88-94	7
α-helix	106-124	19
β-strand	131-133	3	31
β-strand	148	1	32
β-strand	151	1	32
α-helix	155-164	10
β-strand	170-174	5	31
α-helix	181-186	6
β-strand	193-200	8	31
β-strand	216	1	33
β-strand	219	1	33
β-strand	223-228	6	31
α-helix	234-251	18
β-strand	256-260	5	31
β-strand	266	1	34
β-strand	276	1	34
α-helix	278-289	12
β-strand	295-298	4	31
α-helix	305-320	16
α-helix	350-352	3
α-helix	356-371	16
α-helix	374-375	2

Chain D: 8 helices, 1 β-strand

Element	Residues	Length	Sheet
α-helix	11-13	3
α-helix	19-23	5
β-strand	30-34	5	31
α-helix	42-54	13
α-helix	60-69	10
α-helix	74-80	7
α-helix	93-106	14
α-helix	110-116	7
α-helix	122-132	11

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Isoform 2 of Kelch repeat and BTB domain-containing protein 4	A, B	protein	534	Homo sapiens	Q9NVX7 (AlphaFold model)
Histone deacetylase 1	C	protein	482	Homo sapiens	Q13547 (AlphaFold model)
REST corepressor 1	D	protein	401	Homo sapiens	Q9UKL0 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>8VOJ_1 Isoform 2 of Kelch repeat and BTB domain-containing protein 4 (chains A, B)
MKGGNADSWQREKLASMESPEEPGASMDENYFVNYTFKDRSHSGRVAQGIMKLCLEEELF
ADVTISVEGREFQLHRLVLSAQSCFFRSMFTSNLKEAHNRVIVLQDVSESVFQLLVDYIY
HGTVKLRAEELQEIYEVSDMYQLTSLFEECSRFLARTVQVGNCLQVMWLADRHSDPELYT
AAKHCAKTHLAQLQNTEEFLHLPHRLLTDIISDGVPCSQNPTEAIEAWINFNKEEREAFA
ESLRTSLKEIGENVHIYLIGKESSRTHSLAVSLHCAEDDSISVSGQNSLCHQITAACKHG
GDLYVVGGSIPRRMWKCNNATVDWEWCAPLPRDRLQHTLVSVPGKDAIYSLGGKTLQDTL
SNAVIYYRVGDNVWTETTQLEVAVSGAAGANLNGIIYLLGGEENDLDFFTKPSRLIQCFD
TETDKCHVKPYVLPFAGRMHAAVHKDLVFIVAEGDSLVCYNPLLDSFTRLCLPEAWSSAP
SLWKIASCNGSIYVFRDRYKKGDANTYKLDPATSAVTVTRGIKVLLTNLQFVLA

Sequence of entity 2 (C), FASTA

>8VOJ_2 Histone deacetylase 1 (chains C)
MAQTQGTRRKVCYYYDGDVGNYYYGQGHPMKPHRIRMTHNLLLNYGLYRKMEIYRPHKAN
AEEMTKYHSDDYIKFLRSIRPDNMSEYSKQMQRFNVGEDCPVFDGLFEFCQLSTGGSVAS
AVKLNKQQTDIAVNWAGGLHHAKKSEASGFCYVNDIVLAILELLKYHQRVLYIDIDIHHG
DGVEEAFYTTDRVMTVSFHKYGEYFPGTGDLRDIGAGKGKYYAVNYPLRDGIDDESYEAI
FKPVMSKVMEMFQPSAVVLQCGSDSLSGDRLGCFNLTIKGHAKCVEFVKSFNLPMLMLGG
GGYTIRNVARCWTYETAVALDTEIPNELPYNDYFEYFGPDFKLHISPSNMTNQNTNEYLE
KIKQRLFENLRMLPHAPGVQMQAIPEDAIPEESGDEDEDDPDKRISICSSDKRIACEEEF
SDSEEEGEGGRKNSSNFKKAKRVKTEDEKEKDPEEKKEVTEEEKTKEEKPEAKGVKEEVK
LA

Sequence of entity 3 (D), FASTA

>8VOJ_3 REST corepressor 1 (chains D)
MSWEEGSSGSSSDEEHGGGGMRVGPQYQAVVPDFDPAKLARRSQERDNLGMLVWSPNQNL
SEAKLDEYIAIAKEKHGYNMEQALGMLFWHKHNIEKSLADLPNFTPFPDEWTVEDKVLFE
QAFSFHGKTFHRIQQMLPDKSIASLVKFYYSWKKTRTKTSVMDRHARKQKREREESEDEL
EEANGNNPIDIEVDQNKESKKEVPPTETVPQVKKEKHSTQAKNRAKRKPPKGMFLSQEDV
EAVSANATAATTVLRQLDMELVSVKRQIQNIKQTNSALKEKLDGGIEPYRLPEVIQKCNA
RWTTEEQLLAVQAIRKYGRDFQAISDVIGNKSVVQVKNFFVNYRRRFNIDEVLQEWEAEH
GKEETNGPSNQKPVKSPDNSIKMPEEEDEAPVLDVRYASAS

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
IHP	Inositol hexakisphosphate	C6 H18 O24 P6	1
ZN	Zinc ion	Zn	1

Primary citation

UM171 glues asymmetric CRL3-HDAC1/2 assembly to degrade CoREST corepressors. Yeo, M.J.R., Zhang, O., Xie, X. et al. Nature (2025) 639:232-240. DOI 10.1038/s41586-024-08532-4 · 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
9I2C 3.3 Å, Cryo-EM structure of KBTBD4 WT-HDAC2-CoREST1 2:1:1 complex mediated by molecular glue…
8VRT 3.42 Å, The structure of LSD1-CoREST-HDAC1 in complex with KBTBD4R313PRR mutant
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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