7ZR5: HSP90-CDC37-BRAF(V600E)-PP5(closed) complex

CryoEM structure of HSP90-CDC37-BRAF(V600E)-PP5(closed) complex. Determined by electron microscopy at 3.9 Å resolution. Released 14 Dec 2022.

Method: Electron microscopy
Resolution: 3.9 Å
Organism: Homo sapiens
Chains: 5
Atoms: 17,518
Mol. weight: 367.27 kDa
Ligands: ATP
Released: 14 Dec 2022

Explore 7ZR5 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7ZR5 contains 96 α-helices and 93 β-strands across 5 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: 24 helices, 32 β-strands

Element	Residues	Length	Sheet
β-strand	13-14	2	1
β-strand	18-19	2	2
α-helix	21-30	10
α-helix	38-60	23
β-strand	73	1	3
β-strand	76-78	3	3
β-strand	83-85	3	3
β-strand	88	1	3
α-helix	95-100	6
β-strand	104-105	2	4
α-helix	110-114	5
α-helix	134-138	5
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	195-204	10
β-strand	213	1	3
α-helix	288-290	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	379-383	5	5
β-strand	388	1	6
β-strand	395	1	6
α-helix	400-419	20
α-helix	425-432	8
α-helix	434-443	10
α-helix	448-451	4
α-helix	452-454	3
β-strand	456-457	2	7
β-strand	467-468	2	7
α-helix	469-473	5
β-strand	483-487	5	8
α-helix	491-495	5
β-strand	511-513	3	8
α-helix	516-522	7
β-strand	527-528	2	9
β-strand	531-532	2	9
β-strand	533-535	3	8
α-helix	547-559	13
α-helix	562-571	10
β-strand	578-580	3	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	626-628	3	10
α-helix	633-644	12
α-helix	649-664	16
α-helix	673-687	15

Chain B: 27 helices, 38 β-strands

Element	Residues	Length	Sheet
β-strand	14	1	3
β-strand	18-19	2	4
α-helix	22-30	9
α-helix	39-58	20
α-helix	62-65	4
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	134-139	6
β-strand	142-147	6	1
β-strand	155-159	5	1
β-strand	165-169	5	1
α-helix	174-175	2
β-strand	179-184	6	1
α-helix	195-204	10
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	1	15
β-strand	330	1	14
β-strand	333-335	3	13
α-helix	349-350	2
β-strand	353	1	16
β-strand	356	1	17
β-strand	357	1	15
β-strand	361	1	17
β-strand	379	1	16
β-strand	383	1	15
β-strand	388	1	18
β-strand	395	1	18
α-helix	399-419	21
α-helix	426-430	5
α-helix	434-442	9
α-helix	450-452	3
β-strand	457	1	19
β-strand	458-459	2	20
β-strand	467	1	19
α-helix	469-474	6
β-strand	483-487	5	20
α-helix	491-495	5
α-helix	500-503	4
α-helix	504-506	3
β-strand	511-513	3	20
α-helix	517-524	8
β-strand	527-528	2	21
β-strand	531-532	2	21
β-strand	533-535	3	20
β-strand	538	1	22
α-helix	547-559	13
α-helix	561-570	10
β-strand	575-580	6	23
β-strand	589-592	4	23
β-strand	593	1	22
α-helix	600-607	8
α-helix	617-620	4
α-helix	621-623	3
β-strand	624-628	5	23
α-helix	633-644	12
α-helix	649-665	17
α-helix	673-687	15

Chain C: 12 helices, 5 β-strands

Element	Residues	Length	Sheet
α-helix	5-7	3
β-strand	10	1	24
β-strand	23	1	25
α-helix	27-71	45
α-helix	79-111	33
β-strand	114	1	24
α-helix	116-119	4
β-strand	120-124	5	14
β-strand	127-128	2	13
α-helix	140-146	7
α-helix	147-152	6
α-helix	153-163	11
α-helix	168-181	14
α-helix	184-200	17
α-helix	203-226	24
α-helix	235-242	8
α-helix	246-264	19

Chain K: 10 helices, 4 β-strands

Element	Residues	Length	Sheet
β-strand	535-536	2	26
α-helix	537-538	2
α-helix	539-543	5
α-helix	550-567	18
α-helix	568-570	3
α-helix	579-581	3
β-strand	583-584	2	26
β-strand	590-591	2	26
β-strand	592	1	25
α-helix	635-651	17
α-helix	662-670	9
α-helix	687-696	10
α-helix	704-706	3
α-helix	707-718	12

Chain P: 23 helices, 14 β-strands

Element	Residues	Length	Sheet
α-helix	29-31	3
α-helix	32-35	4
α-helix	37-40	4
α-helix	44-57	14
α-helix	62-73	12
α-helix	79-90	12
α-helix	96-109	14
α-helix	114-120	7
α-helix	134-150	17
α-helix	188-199	12
α-helix	203-205	3
α-helix	206-220	15
β-strand	226-229	4	27
β-strand	237-240	4	28
α-helix	247-257	11
β-strand	266-268	3	28
α-helix	279-292	14
β-strand	297-299	3	28
α-helix	303-305	3
α-helix	307-310	4
α-helix	315-322	8
α-helix	325-335	11
β-strand	341-344	4	27
β-strand	348-351	4	27
α-helix	363-367	5
α-helix	374-376	3
α-helix	380-386	7
β-strand	388-389	2	29
β-strand	396-397	2	29
β-strand	404-406	3	29
α-helix	408-418	11
β-strand	422-424	3	27
β-strand	434-437	4	27
α-helix	438-440	3
β-strand	442-445	4	27
β-strand	459-464	6	28
β-strand	472-476	5	28

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)
Serine/threonine-protein phosphatase 5	P	protein	489	Homo sapiens	P53041 (AlphaFold model)

Sequence of entity 1 (A, B), FASTA

>7ZR5_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

>7ZR5_2 Hsp90 co-chaperone Cdc37 (chains C)
MVDYSVWDHIEVSDDEDETHPNIDTASLFRWRHQARVERMEQFQKEKEELDRGCRECKRK
VAECQRKLKELEVAEGGKAELERLQAEAQQLRKEERSWEQKLEEMRKKEKSMPWNVDTLS
KDGFSKSMVNTKPEKTEEDSEEVREQKHKTFVEKYEKQIKHFGMLRRWDDSQKYLSDNVH
LVCEETANYLVIWCIDLEVEEKCALMEQVAHQTIVMQFILELAKSLKVDPRACFRQFFTK
IKTADRQYMEGFNDELEAFKERVRGRAKLRIEKAMKEYEEEERKKRLGPGGLDPVEVYES
LPEELQKCFDVKDVQMLQDAISKMDPTDAKYHMQRCIDSGLWVPNSKASEAKEGEEAGPG
DPLLEAVPKTGDEKDVSVLEVLFQGPLEHHHHHHHH

Sequence of entity 3 (K), FASTA

>7ZR5_3 Serine/threonine-protein kinase B-raf (chains K)
MGGSHHHHHHHHGGSWSHPQFEKGGGSGGGSGGGSWSHPQFEKGAETAVPNSLEVLFQGP
SAMAALSGGGGGGAEPGQALFNGDMEPEAGAGAGAAASSAADPAIPEEVWNIKQMIKLTQ
EHIEALLDKFGGEHNPPSIYLEAYEEYTSKLDALQQREQQLLESLGNGTDFSVSSSASMD
TVTSSSSSSLSVLPSSLSVFQNPTDVARSNPKSPQKPIVRVFLPNKQRTVVPARCGVTVR
DSLKKALMMRGLIPECCAVYRIQDGEKKPIGWDTDISWLTGEELHVEVLENVPLTTHNFV
RKTFFTLAFCDFCRKLLFQGFRCQTCGYKFHQRCSTEVPLMCVNYDQLDLLFVSKFFEHH
PIPQEEASLAETALTSGSSPSAPASDSIGPQILTSPSPSKSIPIPQPFRPADEDHRNQFG
QRDRSSSAPNVHINTIEPVNIDDLIRDQGFRGDGGSTTGLSATPPASLPGSLTNVKALQK
SPGPQRERKSSSSSEDRNRMKTLGRRDSSDDWEIPDGQITVGQRIGSGSFGTVYKGKWHG
DVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLY
HHLHIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLA
TEKSRWSGSHQFEQLSGSILWMAPEVIRMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSN
INNRDQIIFMVGRGYLSPDLSKVRSNCPKAMKRLMAECLKKKRDERPLFPQILASIELLA
RSLPKIHRSASEPSLNRAGFQTEDFSLYACASPKTPIQAGGYGAFPVH

Sequence of entity 4 (P), FASTA

>7ZR5_4 Serine/threonine-protein phosphatase 5 (chains P)
DEPPADGALKRAEELKTQANDYFKAKDYENAIKFYSQAIELNPSNAIYYGNRSLAYLRTE
CYGYALGDATRAIELDKKYIKGYYRRAASNMALGKFRAALRDYETVVKVKPHDKDAKMKY
QECNKIVKQKAFERAIAGDEHKRSVVDSLDIESMTIEDEYSGPKLEDGKVTISFMKELMQ
WYKDQKKLHRKCAYQILVQVKEVLSKLSTLVETTLKETEKITVCGDTHGQFYDLLNIFEL
NGLPSETNPYIFNGDFVDRGSFSVEVILTLFGFKLLYPDHFHLLRGNHETDNMNQIYGFE
GEVKAKYTAQMYELFSEVFEWLPLAQCINGKVLIMHGGLFSEDGVTLDDIRKIERNRQPP
DSGPMCDLLWSDPQPQNGRSISKRGVSCQFGPDVTKAFLEENNLDYIIRSHEVKAEGYEV
AHGGRCVTVFSAPNYCDQMGNKASYIHLQGSDLRPQFHQFTAVPHPNVKPMAYANTLLQL
GMMHHHHHH

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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