8PVY: Human BRISC dimer complex

Cryo-EM structure of the human BRISC dimer complex bound to compound FX-171-C. Determined by electron microscopy at 3.02 Å resolution. Released 12 Feb 2025.

Method: Electron microscopy
Resolution: 3.02 Å
Organism: Homo sapiens
Chains: 16
Atoms: 35,736
Mol. weight: 560.96 kDa
Ligands: ZN, G1V
Released: 12 Feb 2025

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

Secondary structure: helices and β-sheets

8PVY contains 168 α-helices and 162 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: 9 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	11-15	5	1
α-helix	16-26	11
β-strand	35-42	8	1
β-strand	71-80	10	1
α-helix	94-111	18
β-strand	116-125	10	1
α-helix	131-132	2
α-helix	133-145	13
β-strand	150-160	11	1
β-strand	165-174	10	1
β-strand	212-213	2	1
β-strand	216-219	4	1
α-helix	226-233	8
α-helix	235-251	17
α-helix	258-275	18
α-helix	276-280	5
α-helix	281-311	31

Chain B: 8 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	2-5	4	1
α-helix	7-18	12
β-strand	24-34	11	1
β-strand	52-61	10	1
β-strand	69	1	2
β-strand	75	1	2
α-helix	77-83	7
α-helix	87-89	3
β-strand	91-99	9	1
α-helix	107-120	14
β-strand	126-133	8	1
β-strand	141-148	8	1
β-strand	157-158	2	1
β-strand	160-161	2	1
α-helix	165-167	3
α-helix	177-179	3
α-helix	183-192	10
β-strand	197	1	3
β-strand	203	1	3
α-helix	204-251	48

Chain C: 8 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	11-15	5	4
α-helix	16-26	11
β-strand	35-42	8	4
β-strand	71-79	9	4
α-helix	94-111	18
β-strand	116-125	10	4
α-helix	133-145	13
β-strand	150-160	11	4
β-strand	165-174	10	4
β-strand	212-213	2	4
β-strand	216-219	4	4
α-helix	226-232	7
α-helix	234-251	18
α-helix	258-275	18
α-helix	276-280	5
α-helix	281-310	30

Chain D: 9 helices, 10 β-strands

Element	Residues	Length	Sheet
β-strand	2-5	4	4
α-helix	7-17	11
β-strand	24-30	7	4
β-strand	53-61	9	4
β-strand	69	1	5
β-strand	75	1	5
α-helix	77-83	7
α-helix	87-89	3
β-strand	91-99	9	4
α-helix	107-120	14
β-strand	126-134	9	4
β-strand	140-148	9	4
β-strand	157-158	2	4
β-strand	160-161	2	4
α-helix	165-167	3
α-helix	177-179	3
α-helix	183-191	9
α-helix	193-195	3
α-helix	204-251	48

Chain E: 11 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	3-7	5
β-strand	10	1	6
α-helix	15-23	9
β-strand	36-41	6	7
β-strand	53	1	6
β-strand	55-59	5	7
β-strand	61-62	2	8
β-strand	65-66	2	8
β-strand	69-72	4	7
β-strand	83-85	3	7
α-helix	112-132	21
α-helix	136-147	12
α-helix	149-153	5
β-strand	155	1	9
α-helix	159-161	3
β-strand	175-176	2	9
β-strand	201-204	4	9
β-strand	218-221	4	9
α-helix	223-226	4
α-helix	231-233	3
α-helix	238-241	4
α-helix	250-279	30
α-helix	378-380	3

Chain F: 11 helices, 12 β-strands

Element	Residues	Length	Sheet
α-helix	4-7	4
β-strand	10	1	10
α-helix	12-14	3
α-helix	15-23	9
β-strand	36-41	6	11
β-strand	53	1	10
β-strand	55-59	5	11
β-strand	61-62	2	12
β-strand	65-66	2	12
β-strand	69-72	4	11
β-strand	83-85	3	11
α-helix	100-103	4
α-helix	112-132	21
α-helix	136-146	11
α-helix	160-162	3
β-strand	175-176	2	13
β-strand	201-203	3	13
β-strand	219-221	3	13
α-helix	223-227	5
α-helix	238-241	4
α-helix	246-278	33
β-strand	299	1	14
α-helix	358-361	4

Chain G: 8 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	11-15	5	15
α-helix	16-26	11
β-strand	35-42	8	15
β-strand	71-79	9	15
α-helix	94-111	18
β-strand	117-125	9	15
α-helix	131-132	2
α-helix	133-146	14
β-strand	150-160	11	15
β-strand	165-174	10	15
β-strand	212-213	2	15
β-strand	216-219	4	15
α-helix	226-251	26
α-helix	258-275	18
α-helix	276-280	5
α-helix	281-311	31

Chain H: 9 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	2-5	4	16
α-helix	7-19	13
β-strand	24-34	11	16
β-strand	52-61	10	16
β-strand	69	1	17
β-strand	75	1	17
α-helix	77-83	7
α-helix	87-89	3
β-strand	91-99	9	16
α-helix	107-120	14
β-strand	126-134	9	16
β-strand	141-148	8	16
β-strand	157-158	2	16
α-helix	159	1
β-strand	160-161	2	16
α-helix	165-168	4
α-helix	177-179	3
α-helix	183-192	10
β-strand	197	1	18
β-strand	203	1	18
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	312	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

>8PVY_1 Lys-63-specific deubiquitinase BRCC36 (chains A, C, G, I)
MAVQVVQAVQAVHLESDAFLVCLNHALSTEKEEVMGLCIGELNDDTRSDSKFAYTGTEMR
TVAEKVDAVRIVHIHSVIILRRSDKRKDRVEISPEQLSAASTEAERLAELTGRPMRVVGW
YHSHPHITVWPSHVDVRTQAMYQMMDQGFVGLIFSCFIEDKNTKTGRVLYTCFQSIQAQK
SSESLHGPRDFWSSSQHISIEGQKEEERYERIEIPIHIVPHVTIGKVCLESAVELPKILC
QEEQDAYRRIHSLTHLDSVTKIHNGSVFTKNLCSQMSAVSGPLLQWLEDRLEQNQQHLQE
LQQEKEELMQEL

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

>8PVY_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

>8PVY_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

>8PVY_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
ZN	Zinc ion	Zn	4
G1V	N-[(1R,5S)-3-azabicyclo[3.1.0]hexan-6-yl]-1-[2,6-bis(chloranyl)phenyl]carbonyl-…	C23 H17 Cl4 N5 O3	2

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
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
8PY2 3.32 Å, Cryo-EM structure of the human BRISC dimer complex bound to compound JMS-175-2
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

Browse structure collections

About this viewer

MolViewer shows 8PVY directly in your browser with nothing to install. Switch between cartoon, ball-and-stick, spacefill and surface views, color by chain, secondary structure or B-factor, measure distances, angles and dihedrals, and share or embed the view.