8PY2: Human BRISC dimer complex

Cryo-EM structure of the human BRISC dimer complex bound to compound JMS-175-2. Determined by electron microscopy at 3.32 Å resolution. Released 5 Feb 2025.

Method: Electron microscopy
Resolution: 3.32 Å
Organism: Homo sapiens
Chains: 16
Atoms: 35,730
Mol. weight: 562.63 kDa
Ligands: X8C, ZN
Released: 5 Feb 2025

Explore 8PY2 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8PY2 contains 150 α-helices and 191 β-strands across 16 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: 7 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	11-14	4	1
β-strand	15	1	2
α-helix	16-26	11
β-strand	35-40	6	3
β-strand	42	1	1
β-strand	71-74	4	1
β-strand	76-79	4	3
α-helix	94-111	18
β-strand	116-125	10	3
α-helix	133-145	13
β-strand	150-156	7	3
β-strand	158-160	3	3
β-strand	165-175	11	3
β-strand	211-213	3	3
β-strand	216	1	1
β-strand	219	1	2
α-helix	226-251	26
α-helix	258-275	18
α-helix	276-280	5
α-helix	281-310	30

Chain B: 7 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	2-5	4	3
α-helix	7-19	13
β-strand	24-34	11	3
β-strand	52-61	10	3
β-strand	69	1	4
β-strand	75	1	4
α-helix	77-83	7
α-helix	87-90	4
β-strand	91-99	9	3
α-helix	107-120	14
β-strand	126-134	9	3
β-strand	141-148	8	3
β-strand	157-158	2	3
β-strand	160-161	2	3
α-helix	169-173	5
α-helix	183-192	10
β-strand	197	1	5
β-strand	203	1	5
α-helix	204-251	48

Chain C: 7 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	11	1	6
β-strand	12-15	4	7
α-helix	16-26	11
β-strand	35-40	6	8
β-strand	71	1	6
β-strand	74	1	7
β-strand	76-79	4	8
α-helix	94-111	18
β-strand	116-125	10	8
α-helix	133-145	13
β-strand	150-159	10	8
β-strand	166-170	5	8
β-strand	172-176	5	8
β-strand	210-213	4	8
β-strand	216-219	4	7
α-helix	226-251	26
α-helix	258-275	18
α-helix	276-280	5
α-helix	281-311	31

Chain D: 6 helices, 15 β-strands

Element	Residues	Length	Sheet
β-strand	2-5	4	9
α-helix	7-18	12
β-strand	24-29	6	8
β-strand	30-32	3	9
β-strand	53-56	4	9
β-strand	60-61	2	8
β-strand	69	1	10
β-strand	75	1	10
α-helix	77-83	7
β-strand	91-97	7	8
α-helix	107-120	14
β-strand	126-130	5	8
β-strand	133-134	2	8
β-strand	141-148	8	8
β-strand	157-158	2	8
β-strand	159-161	3	9
α-helix	165-167	3
α-helix	183-192	10
β-strand	197	1	11
β-strand	203	1	11
α-helix	204-251	48

Chain E: 11 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	3-9	7
β-strand	10	1	12
α-helix	15-23	9
β-strand	36-41	6	13
β-strand	53	1	12
β-strand	55-59	5	13
β-strand	61	1	14
β-strand	66	1	14
β-strand	69-72	4	13
α-helix	81-82	2
β-strand	83-85	3	13
α-helix	100-104	5
α-helix	112-132	21
α-helix	138-147	10
β-strand	155-159	5	15
β-strand	171-175	5	15
β-strand	176	1	16
α-helix	186-188	3
β-strand	202-204	3	16
β-strand	206	1	15
β-strand	218-220	3	16
α-helix	223-228	6
α-helix	231-235	5
α-helix	238-241	4
α-helix	249-282	34

Chain F: 12 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	3-9	7
β-strand	10	1	17
α-helix	15-23	9
β-strand	37-41	5	18
β-strand	53	1	17
β-strand	55-62	8	18
β-strand	65-72	8	18
α-helix	81-82	2
β-strand	83-85	3	18
α-helix	100-103	4
α-helix	112-132	21
α-helix	136-147	12
α-helix	149-152	4
β-strand	155-157	3	19
β-strand	171-176	6	19
β-strand	202-207	6	19
β-strand	216	1	19
β-strand	219-220	2	19
α-helix	223-229	7
α-helix	238-241	4
α-helix	246-282	37
β-strand	308	1	20
α-helix	338-340	3
α-helix	369-372	4

Chain G: 7 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	11-15	5	21
α-helix	16-26	11
β-strand	35-42	8	21
β-strand	71-80	10	21
α-helix	94-111	18
β-strand	117-123	7	21
α-helix	133-145	13
β-strand	150-160	11	21
β-strand	165-176	12	21
β-strand	210-213	4	21
β-strand	217-219	3	21
α-helix	226-251	26
α-helix	258-275	18
α-helix	276-280	5
α-helix	281-311	31

Chain H: 6 helices, 14 β-strands

Element	Residues	Length	Sheet
β-strand	2-5	4	22
α-helix	7-18	12
β-strand	24-33	10	22
β-strand	53-61	9	22
β-strand	69	1	23
β-strand	75	1	23
α-helix	77-83	7
α-helix	88-90	3
β-strand	91-98	8	22
α-helix	107-120	14
β-strand	126-131	6	22
β-strand	134	1	24
β-strand	141	1	24
β-strand	144-148	5	22
β-strand	157-158	2	22
β-strand	160-161	2	22
α-helix	183-192	10
β-strand	197	1	25
β-strand	203	1	25
α-helix	204-251	48

8 more chain groups are not listed. Open the entry in the viewer and use the sequence panel to see them.

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Lys-63-specific deubiquitinase BRCC36	A, C, G, I	protein	316	Homo sapiens	P46736 (AlphaFold model)
BRISC complex subunit Abraxas 2	B, D, H, J	protein	267	Homo sapiens	Q15018 (AlphaFold model)
BRISC and BRCA1-A complex member 2	E, F, K, L	protein	385	Homo sapiens	Q9NXR7 (AlphaFold model)
BRISC and BRCA1-A complex member 1	M, N, O, P	protein	259	Homo sapiens	Q9NWV8 (AlphaFold model)

Sequence of entity 1 (A, C, G, I), FASTA

>8PY2_1 Lys-63-specific deubiquitinase BRCC36 (chains A, C, G, I)
MAVQVVQAVQAVHLESDAFLVCLNHALSTEKEEVMGLCIGELNDDTRSDSKFAYTGTEMR
TVAEKVDAVRIVHIHSVIILRRSDKRKDRVEISPEQLSAASTEAERLAELTGRPMRVVGW
YHSHPHITVWPSHVDVRTQAMYQMMDQGFVGLIFSCFIEDKNTKTGRVLYTCFQSIQAQK
SSESLHGPRDFWSSSQHISIEGQKEEERYERIEIPIHIVPHVTIGKVCLESAVELPKILC
QEEQDAYRRIHSLTHLDSVTKIHNGSVFTKNLCSQMSAVSGPLLQWLEDRLEQNQQHLQE
LQQEKEELMQELSSLE

Sequence of entity 2 (B, D, H, J), FASTA

>8PY2_2 BRISC complex subunit Abraxas 2 (chains B, D, H, J)
MAASISGYTFSAVCFHSANSNADHEGFLLGEVRQEETFSISDSQISNTEFLQVIEIHNHQ
PCSKLFSFYDYASKVNEESLDRILKDRRKKVIGWYRFRRNTQQQMSYREQVLHKQLTRIL
GVPDLVFLLFSFISTANNSTHALEYVLFRPNRRYNQRISLAIPNLGNTSQQEYKVSSVPN
TSQSYAKVIKEHGTDFFDKDGVMKDIRAIYQVYNALQEKVQAVCADVEKSERVVESCQAE
VNKLRRQITQRKNEKEQERRLQQAVLS

Sequence of entity 3 (E, F, K, L), FASTA

>8PY2_3 BRISC and BRCA1-A complex member 2 (chains E, F, K, L)
GAMSPEVALNRISPMLSPFISSVVRNGKVGLDATNCLRITDLKSGCTSLTPGPNCDRFKL
HIPYAGETLKWDIIFNAQYPELPPDFIFGEDAEFLPDPSALQNLASWNPSNPECLLLVVK
ELVQQYHQFQCSRLRESSRLMFEYQTLLEEPQYGENMEIYAGKKNNWTGEFSARFLLKLP
VDFSNIPTYLLKDVNEDPGEDVALLSVSFEDTEATQVYPKLYLSPRIEHALGGSSALHIP
AFPGGGCLIDYVPQVCHLLTNKVQYVIQGYHKRREYIAAFLSHFGTGVVEYDAEGFTKLT
LLLMWKDFCFLVHIDLPLFFPRDQPTLTFQSVYHFTNSGQLYSQAQKNYPYSPRWDGNEM
AKRAKAYFKTFVPQFQEAAFANGKL

Sequence of entity 4 (M, N, O, P), FASTA

>8PY2_4 BRISC and BRCA1-A complex member 1 (chains M, N, O, P)
MSWQVPPPAPEVQIRTPRVNCPEKVIICLDLSEEMSLPKLESFNGSKTNALNVSQKMIEM
FVRTKHKIDKSHEFALVVVNDDTAWLSGLTSDPRELCSCLYDLETASCSTFNLEGLFSLI
QQKTELPVTENVQTIPPPYVVRTILVYSRPPCQPQFSLTEPMKKMFQCPYFFFDVVYIHN
GTEEKEEEMSWKDMFAFMGSLDTKGTSYKYEVALAGPALELHNCMAKLLAHPLQRPCQSH
ASYSLLEEEDEAIEVEATV

Ligands and cofactors

ID	Name	Formula	Copies
X8C	1-[2,6-bis(chloranyl)phenyl]carbonyl-4-[[2,6-bis(chloranyl)phenyl]carbonylamino…	C23 H19 Cl4 N5 O3	2
ZN	Zinc ion	Zn	4

Primary citation

Molecular glues that inhibit deubiquitylase activity and inflammatory signaling. Chandler, F., Reddy, P.A.N., Bhutda, S. et al. Nat Struct Mol Biol (2025). DOI 10.1038/s41594-025-01517-5 · PubMed

Other PDB entries of the same protein (UniProt P46736 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9SQY 2.92 Å, Cryo-EM structure of the ARISC(E33A)-RAP80:K63-Ub7 complex (Composite map)
9SMP 3.0 Å, BRCA1-A complex bound to K63-polyUbATA - open form double State P
8PVY 3.02 Å, Cryo-EM structure of the human BRISC dimer complex bound to compound FX-171-C
9SMN 3.2 Å, BRCA1-A complex bound to K63-polyUbATA - open form StateC StateP
9SNA 3.2 Å, BRCA1-A complex bound to K63-diUbATA - open form StateC StateP
9SQW 3.2 Å, Cryo-EM structure of the ARISCdC(E33A):K63-Ub7 complex (Composite map)
9SQV 3.21 Å, Cryo-EM structure of the ARISCdC(E33A):K63-Ub4 complex (Composite map)
9SMR 3.25 Å, Structure of apo BRCA1-A complex in presence of K63-oligoUbATA
9SO9 3.4 Å, BRCA1-A complex bound to K63-oligoUbATA - closed form StateC*
6R8F 3.8 Å, Cryo-EM structure of the Human BRISC-SHMT2 complex
6H3C 3.9 Å, Cryo-EM structure of the BRISC complex bound to SHMT2

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