7ZR0: HSP90-CDC37-BRAF(V600E) complex

CryoEM structure of HSP90-CDC37-BRAF(V600E) complex. Determined by electron microscopy at 3.4 Å resolution. Released 14 Dec 2022.

Method: Electron microscopy
Resolution: 3.4 Å
Organism: Homo sapiens
Chains: 4
Atoms: 14,052
Mol. weight: 311.25 kDa
Ligands: ATP
Released: 14 Dec 2022

Explore 7ZR0 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7ZR0 contains 66 α-helices and 75 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: 23 helices, 31 β-strands

Element	Residues	Length	Sheet
β-strand	13-16	4	1
β-strand	18-19	2	2
α-helix	21-30	10
α-helix	38-60	23
β-strand	73-78	6	3
β-strand	83-85	3	3
β-strand	88	1	3
β-strand	104-105	2	4
α-helix	110-116	7
α-helix	134-137	4
β-strand	140-148	9	3
β-strand	155-159	5	3
β-strand	166	1	3
β-strand	169	1	3
β-strand	178-185	8	3
α-helix	196-205	10
β-strand	213-215	3	3
α-helix	285-287	3
α-helix	293-295	3
α-helix	298-306	9
β-strand	318-324	7	5
β-strand	328-334	7	5
β-strand	353-357	5	5
β-strand	361	1	5
β-strand	378-383	6	5
β-strand	388	1	6
β-strand	395	1	6
α-helix	400-419	20
α-helix	425-432	8
α-helix	437-440	4
α-helix	448-451	4
β-strand	456-457	2	7
β-strand	467-468	2	7
α-helix	469-473	5
β-strand	482-487	6	8
α-helix	492-495	4
α-helix	503-506	4
β-strand	510-513	4	8
α-helix	516-522	7
β-strand	528	1	9
β-strand	531	1	9
β-strand	532-535	4	8
α-helix	547-556	10
α-helix	562-571	10
β-strand	579-580	2	10
β-strand	589-590	2	10
β-strand	593	1	11
α-helix	600-608	9
α-helix	614-617	4
β-strand	624	1	11
β-strand	627-628	2	10
α-helix	633-644	12
α-helix	650-664	15
α-helix	673-686	14

Chain B: 23 helices, 36 β-strands

Element	Residues	Length	Sheet
β-strand	14	1	3
β-strand	18-19	2	4
α-helix	22-31	10
α-helix	39-58	20
α-helix	62-64	3
β-strand	73-75	3	12
β-strand	76-78	3	1
β-strand	83-85	3	1
β-strand	88	1	12
α-helix	95-102	8
β-strand	104-105	2	2
α-helix	109-116	8
α-helix	133-139	7
β-strand	142-148	7	1
β-strand	154-159	6	1
β-strand	164-169	6	1
β-strand	179-184	6	1
α-helix	195-205	11
β-strand	213-215	3	12
α-helix	299-306	8
β-strand	317-319	3	13
β-strand	322-325	4	14
β-strand	329-330	2	14
β-strand	334-335	2	13
α-helix	343-345	3
α-helix	349-350	2
β-strand	353-356	4	15
β-strand	357	1	14
β-strand	361-364	4	15
β-strand	378	1	13
β-strand	379-380	2	15
β-strand	383	1	14
β-strand	388	1	16
β-strand	395	1	16
α-helix	399-419	21
α-helix	426-430	5
α-helix	434-442	9
β-strand	456-459	4	17
β-strand	462-468	7	17
α-helix	469-474	6
β-strand	483-487	5	17
α-helix	500-503	4
β-strand	511-513	3	17
α-helix	517-524	8
β-strand	527-528	2	18
β-strand	531-532	2	18
β-strand	533-535	3	17
β-strand	538	1	19
α-helix	547-559	13
α-helix	563-570	8
β-strand	573	1	19
β-strand	575-580	6	19
β-strand	589-593	5	19
α-helix	600-606	7
α-helix	617-620	4
β-strand	624-628	5	19
α-helix	633-644	12
α-helix	649-665	17
α-helix	673-686	14

Chain C: 12 helices, 5 β-strands

Element	Residues	Length	Sheet
β-strand	10	1	20
β-strand	23	1	21
α-helix	27-71	45
α-helix	79-111	33
α-helix	113	1
β-strand	114	1	20
α-helix	116-119	4
β-strand	120-122	3	14
β-strand	127-128	2	13
α-helix	140-146	7
α-helix	147-152	6
α-helix	153-163	11
α-helix	169-181	13
α-helix	184-200	17
α-helix	203-226	24
α-helix	235-242	8
α-helix	246-265	20

Chain K: 8 helices, 3 β-strands

Element	Residues	Length	Sheet
α-helix	534-535	2
β-strand	536	1	22
α-helix	537-538	2
α-helix	539-543	5
α-helix	550-567	18
β-strand	583	1	22
β-strand	592	1	21
α-helix	635-651	17
α-helix	662-670	9
α-helix	688-696	9
α-helix	707-718	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Heat shock protein HSP 90-beta	A, B	protein	749	Homo sapiens	P08238 (AlphaFold model)
Hsp90 co-chaperone Cdc37	C	protein	396	Homo sapiens	Q16543 (AlphaFold model)
Serine/threonine-protein kinase B-raf	K	protein	828	Homo sapiens	P15056 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7ZR0_1 Heat shock protein HSP 90-beta (chains A, B)
MRGSHHHHHHHHGMALEVLFQGPSAMPEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSN
KEIFLRELISNASDALDKIRYESLTDPSKLDSGKELKIDIIPNPQERTLTLVDTGIGMTK
ADLINNLGTIAKSGTKAFMEALQAGADISMIGQFGVGFYSAYLVAEKVVVITKHNDDEQY
AWESSAGGSFTVRADHGEPIGRGTKVILHLKEDQTEYLEERRVKEVVKKHSQFIGYPITL
YLEKEREKEISDDEAEEEKGEKEEEDKDDEEKPKIEDVGSDEEDDSGKDKKKKTKKIKEK
YIDQEELNKTKPIWTRNPDDITQEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFI
PRRAPFDLFENKKKKNNIKLYVRRVFIMDSCDELIPEYLNFIRGVVDSEDLPLNISREML
QQSKILKVIRKNIVKKCLELFSELAEDKENYKKFYEAFSKNLKLGIHEDSTNRRRLSELL
RYHTSQSGDEMTSLSEYVSRMKETQKSIYYITGESKEQVANSAFVERVRKRGFEVVYMTE
PIDEYCVQQLKEFDGKSLVSVTKEGLELPEDEEEKKKMEESKAKFENLCKLMKEILDKKV
EKVTISNRLVSSPCCIVTSTYGWTANMERIMKAQALRDNSTMGYMMAKKHLEINPDHPIV
ETLRQKAEADKNDKAVKDLVVLLFETALLSSGFSLEDPQTHSNRIYRMIKLGLGIDEDEV
AAEEPNAAVPDEIPPLEGDEDASRMEEVD

Sequence of entity 2 (C), FASTA

>7ZR0_2 Hsp90 co-chaperone Cdc37 (chains C)
MVDYSVWDHIEVSDDEDETHPNIDTASLFRWRHQARVERMEQFQKEKEELDRGCRECKRK
VAECQRKLKELEVAEGGKAELERLQAEAQQLRKEERSWEQKLEEMRKKEKSMPWNVDTLS
KDGFSKSMVNTKPEKTEEDSEEVREQKHKTFVEKYEKQIKHFGMLRRWDDSQKYLSDNVH
LVCEETANYLVIWCIDLEVEEKCALMEQVAHQTIVMQFILELAKSLKVDPRACFRQFFTK
IKTADRQYMEGFNDELEAFKERVRGRAKLRIEKAMKEYEEEERKKRLGPGGLDPVEVYES
LPEELQKCFDVKDVQMLQDAISKMDPTDAKYHMQRCIDSGLWVPNSKASEAKEGEEAGPG
DPLLEAVPKTGDEKDVSVLEVLFQGPLEHHHHHHHH

Sequence of entity 3 (K), FASTA

>7ZR0_3 Serine/threonine-protein kinase B-raf (chains K)
MGGSHHHHHHHHGGSWSHPQFEKGGGSGGGSGGGSWSHPQFEKGAETAVPNSLEVLFQGP
SAMAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQ
EHIEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMD
TVTSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVR
DSLKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFV
RKTFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHH
PIPQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFG
QRDRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQK
SPGPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHG
DVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLY
HHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLA
TEKSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSN
INNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLA
RSLPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH

Ligands and cofactors

ID	Name	Formula	Copies
ATP	Adenosine-5'-triphosphate	C10 H16 N5 O13 P3	2

Primary citation

HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation. Oberoi, J., Guiu, X.A., Outwin, E.A. et al. Nat Commun (2022) 13:7343-7343. DOI 10.1038/s41467-022-35143-2 · PubMed

Other PDB entries of the same protein (UniProt P08238 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9D9I 1.5 Å, Human Hsp90b nucleotide binding domain in complex with BRI2312
6N8Y 1.55 Å, Hsp90-beta bound to PU-11-trans
5UCJ 1.69 Å, Hsp90b N-terminal domain with inhibitors
7ULJ 1.82 Å, Hsp90b N-terminal domain in complex with 42C
9D9H 1.96 Å, Human Hsp90b nucleotide binding domain in complex with BRI2311
5UC4 2.05 Å, Hsp90b N-terminal domain with inhibitors
3FWV 2.2 Å, Crystal Structure of a Redesigned TPR Protein, T-MOD(VMY), in Complex with MEEVF Peptide
3NMQ 2.2 Å, Hsp90b N-terminal domain in complex with EC44, a pyrrolo-pyrimidine methoxypyridine…
3PRY 2.28 Å, Crystal structure of the middle domain of human HSP90-beta refined at 2.3 A resolution
1UYM 2.45 Å, Human Hsp90-beta with PU3 (9-Butyl-8(3,4,5-trimethoxy-benzyl)-9H-purin-6-ylamine)
3UQ3 2.6 Å, TPR2AB-domain:pHSP90-complex of yeast Sti1
9W5I 2.63 Å, AGO maturation complex (AMC): AGO2-miRNA duplex in complex with Hsp90 beta and…

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