8QU8: Von Hippel-Lindau disease tumor suppressor

PROTAC-mediated complex of KRAS with VHL/Elongin-B/Elongin-C/Cullin-2/Rbx1. Determined by electron microscopy at 3.5 Å resolution. Released 6 Dec 2023.

Method: Electron microscopy
Resolution: 3.5 Å
Organism: Homo sapiens
Chains: 6
Atoms: 10,846
Mol. weight: 169.49 kDa
Ligands: ZN, GDP, WYL
Released: 6 Dec 2023

Explore 8QU8 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8QU8 contains 62 α-helices and 36 β-strands across 6 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: 5 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	73-78	6	1
β-strand	84-88	5	2
β-strand	96	1	2
α-helix	99-100	2
β-strand	101	1	2
α-helix	102	1
β-strand	106-110	5	1
β-strand	117-121	5	2
β-strand	127	1	2
β-strand	129-130	2	1
β-strand	133	1	1
β-strand	142	1	3
β-strand	145	1	3
β-strand	147-152	6	1
α-helix	158-169	12
α-helix	183-189	7
α-helix	194-199	6

Chain B: 4 helices, 7 β-strands

Element	Residues	Length	Sheet
β-strand	3-9	7	4
β-strand	12-18	7	4
β-strand	23	1	5
α-helix	24-35	12
β-strand	43-45	3	4
β-strand	50	1	4
β-strand	56	1	5
α-helix	63-66	4
β-strand	73-78	6	4
α-helix	92-99	8
α-helix	101-103	3

Chain C: 6 helices, 3 β-strands

Element	Residues	Length	Sheet
β-strand	18-22	5	4
β-strand	28-32	5	4
α-helix	33-36	4
α-helix	40-46	7
β-strand	60-61	2	4
α-helix	67-83	17
α-helix	91-94	4
α-helix	97-99	3
α-helix	100-110	11

Chain D: 37 helices, 3 β-strands

Element	Residues	Length	Sheet
α-helix	13-24	12
α-helix	25-27	3
α-helix	32-46	15
α-helix	54-78	25
α-helix	83-104	22
α-helix	106-120	15
α-helix	128-133	6
α-helix	139-152	14
α-helix	155-167	13
α-helix	169-171	3
α-helix	178-190	13
α-helix	201-203	3
α-helix	204-208	5
α-helix	209-227	19
α-helix	232-253	22
α-helix	256-258	3
α-helix	259-270	12
α-helix	275-280	6
α-helix	282-287	6
α-helix	291-303	13
α-helix	308-328	21
α-helix	337-356	20
α-helix	362-376	15
α-helix	387-395	9
α-helix	396-398	3
α-helix	411-422	12
α-helix	428-445	18
α-helix	455-464	10
α-helix	466-494	29
β-strand	507-511	5	6
α-helix	531-548	18
α-helix	553	1
β-strand	554-555	2	6
β-strand	561	1	6
α-helix	611-615	5
α-helix	664-680	17
α-helix	683-690	8
α-helix	696-699	4
α-helix	702-707	6
α-helix	715-726	12

Chain E: 4 helices, 3 β-strands

Element	Residues	Length	Sheet
β-strand	27-32	6	6
α-helix	39-41	3
α-helix	52-53	2
α-helix	55-57	3
β-strand	71-72	2	7
β-strand	78-79	2	7
α-helix	85-90	6

Chain F: 6 helices, 8 β-strands

Element	Residues	Length	Sheet
β-strand	3-10	8	8
α-helix	16-25	10
β-strand	38-46	9	8
β-strand	49-57	9	8
α-helix	66-73	8
β-strand	77-83	7	8
α-helix	87-91	5
α-helix	93-104	12
β-strand	111-116	6	8
α-helix	127-137	11
β-strand	141-143	3	8
β-strand	145	1	9
β-strand	150	1	9
α-helix	152-168	17

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
von Hippel-Lindau disease tumor suppressor	A	protein	212	Homo sapiens	P40337 (AlphaFold model)
Elongin-B	B	protein	117	Homo sapiens	Q15370 (AlphaFold model)
Elongin-C	C	protein	111	Homo sapiens	Q15369 (AlphaFold model)
Cullin-2	D	protein	744	Homo sapiens	Q13617 (AlphaFold model)
E3 ubiquitin-protein ligase RBX1, N-terminally processed	E	protein	107	Homo sapiens	P62877
GTPase KRas	F	protein	170	Homo sapiens	P01116

Sequence of entity 1 (A), FASTA

>8QU8_1 von Hippel-Lindau disease tumor suppressor (chains A)
PRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRP
VLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRD
AGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIV
RSLYEDLEDHPNVQKDLERLTQERIAHQRMGD

Sequence of entity 2 (B), FASTA

>8QU8_2 Elongin-B (chains B)
DVFLMIRRHKTTIFTDAKESSTVFELKRIVEGILKRPPDEQRLYKDDQLLDDGKTLGECG
FTSQTARPQAPATVGLAFRADDTFEALCIEPFSSPPELPDVMKPQDSGSSANEQAVQ

Sequence of entity 3 (C), FASTA

>8QU8_3 Elongin-C (chains C)
DGEEKTYGGCEGPDAMYVKLISSDGHEFIVKREHALTSGTIKAMLSGPGQFAENETNEVN
FREIPSHVLSKVCMYFTYKVRYTNSSTEIPEFPIAPEIALELLMAANFLDC

Sequence of entity 4 (D), FASTA

>8QU8_4 Cullin-2 (chains D)
SLKPRVVDFDETWNKLLTTIKAVVMLEYVERATWNDRFSDIYALCVAYPEPLGERLYTET
KIFLENHVRHLHKRVLESEEQVLVMYHRYWEEYSKGADYMDCLYRYLNTQFIKKNKLTEA
DLQYGYGGVDMNEPLMEIGELALDMWRKLMVEPLQAILIRMLLREIKNDRGGEDPNQKVI
HGVINSFVHVEQYKKKFPLKFYQEIFESPFLTETGEYYKQEASNLLQESNCSQYMEKVLG
RLKDEEIRCRKYLHPSSYTKVIHECQQRMVADHLQFLHAECHNIIRQEKKNDMANMYVLL
RAVSTGLPHMIQELQNHIHDEGLRATSNLTQENMPTLFVESVLEVHGKFVQLINTVLNGD
QHFMSALDKALTSVVNYREPKSVCKAPELLAKYCDNLLKKSAKGMTENEVEDRLTSFITV
FKYIDDKDVFQKFYARMLAKRLIHGLSMSMDSEEAMINKLKQACGYEFTSKLHRMYTDMS
VSADLNNKFNNFIKNQDTVIDLGISFQIYVLQAGAWPLTQAPSSTFAIPQELEKSVQMFE
LFYSQHFSGRKLTWLHYLCTGEVKMNYLGKPYVAMVTTYQMAVLLAFNNSETVSYKELQD
STQMNEKELTKTIKSLLDVKMINHDSEKEDIDAESSFSLNMNFSSKRTKFKITTSMQKDT
PQEMEQTRSAVDEDRKMYLQAAIVRIMKARKVLRHNALIQEVISQSRARFNPSISMIKKC
IEVLIDKQYIERSQASADEYSYVA

Sequence of entity 5 (E), FASTA

>8QU8_5 E3 ubiquitin-protein ligase RBX1, N-terminally processed (chains E)
AAAMDVDTPSGTNSGAGKKRFEVKKWNAVALWAWDIVVDNCAICRNHIMDLCIECQANQA
SATSEECTVAWGVCNHAFHFHCISRWLKTRQVCPLDNREWEFQKYGH

Sequence of entity 6 (F), FASTA

>8QU8_6 GTPase KRas (chains F)
GMTEYKLVVVGAVGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTA
GQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKSD
LPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKEK

Ligands and cofactors

ID	Name	Formula	Copies
ZN	Zinc ion	Zn	2
GDP	Guanosine-5'-diphosphate	C10 H15 N5 O11 P2	1
WYL	(2S,4R)-1-[(2S)-2-[4-[4-[(3S)-4-[4-[5-[(4S)-2-azanyl-3-cyano-4-methyl-6,7-dihyd…	C50 H62 N14 O6 S2	1

Primary citation

Targeting cancer with small-molecule pan-KRAS degraders. Popow, J., Farnaby, W., Gollner, A. et al. Science (2024) 385:1338-1347. DOI 10.1126/science.adm8684 · PubMed

Other PDB entries of the same protein (UniProt P40337 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7Z76 1.32 Å, Crystal structure of compound 10 in complex with the bromodomain of human SMARCA2 and…
9GIO 1.49 Å, Crystal structure of the VHL-EloC-EloB complex with a covalent compound bound to C77 of…
7JTO 1.7 Å, Crystal structure of Protac MS33 in complex with the WD repeat-containing protein 5 and…
8BDS 1.72 Å, Ternary complex between VCB, BRD4-BD1 and PROTAC 48
4AJY 1.73 Å, von Hippel-Lindau protein-ElonginB-ElonginC complex, bound to Hif1- alpha peptide
6GMR 1.75 Å, pVHL:EloB:EloC in complex with (4-(1H-pyrrol-1-yl)phenyl)methanol
6HR2 1.76 Å, Crystal structure of PROTAC 2 in complex with the bromodomain of human SMARCA4 and…
6I7Q 1.8 Å, Structure of pVHL-elongin B-elongin C (VCB) in complex with hydroxylated-HIF-2alpha…
8BB3 1.8 Å, Structure of human WDR5 and pVHL:ElonginC:ElonginB bound to PROTAC with PEG linker…
6GFX 1.83 Å, pVHL:EloB:EloC in complex with modified HIF-1a CODD peptide containing…
1LM8 1.85 Å, Structure of a HIF-1a-pVHL-ElonginB-ElonginC Complex
6ZHC 1.92 Å, PROTAC6 mediated complex of VHL:EloB:EloC and Bcl-xL

Browse structure collections

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