7Z37: RAF1-HSP90-CDC37 complex

Structure of the RAF1-HSP90-CDC37 complex (RHC-II). Determined by electron microscopy at 3.67 Å resolution. Released 14 Sept 2022.

Method: Electron microscopy
Resolution: 3.67 Å
Organism: Homo sapiens
Chains: 4
Atoms: 14,256
Mol. weight: 290.7 kDa
Ligands: ATP
Released: 14 Sept 2022

Explore 7Z37 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7Z37 contains 78 α-helices and 67 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 AP1: 28 helices, 31 β-strands

Element	Residues	Length	Sheet
β-strand	12-14	3	1
β-strand	18-19	2	2
α-helix	21-29	9
α-helix	36-38	3
α-helix	39-60	22
α-helix	62-65	4
β-strand	73-78	6	3
β-strand	83-88	6	3
α-helix	95-103	9
β-strand	104-105	2	4
α-helix	109-117	9
α-helix	133-138	6
β-strand	140-148	9	3
β-strand	155-159	5	3
β-strand	165-167	3	3
β-strand	169	1	3
β-strand	178-185	8	3
α-helix	187-193	7
α-helix	195-204	10
β-strand	213-215	3	3
β-strand	217-222	6	5
β-strand	272-277	6	5
α-helix	293-295	3
α-helix	298-309	12
β-strand	315-325	11	6
β-strand	329-336	8	6
α-helix	346-348	3
β-strand	353-357	5	6
β-strand	361-363	3	6
α-helix	372-374	3
β-strand	378-383	6	6
β-strand	388	1	7
β-strand	395	1	7
α-helix	399-419	21
α-helix	423-443	21
α-helix	448-452	5
β-strand	457-458	2	8
β-strand	459	1	9
α-helix	460-462	3
β-strand	466-467	2	8
α-helix	469-475	7
β-strand	482-487	6	9
α-helix	491-495	5
α-helix	501-505	5
β-strand	511-513	3	9
α-helix	516-521	6
β-strand	527-528	2	9
β-strand	531-535	5	9
β-strand	538	1	10
α-helix	547-559	13
α-helix	562-570	9
β-strand	578-579	2	10
β-strand	589-593	5	10
α-helix	600-607	8
β-strand	624-628	5	10
α-helix	633-644	12
α-helix	649-665	17
α-helix	668-670	3
α-helix	673-688	16

Chain BP1: 28 helices, 31 β-strands

Element	Residues	Length	Sheet
β-strand	13-14	2	3
β-strand	18-19	2	4
α-helix	21-30	10
α-helix	36-38	3
α-helix	39-60	22
α-helix	62-64	3
β-strand	73-78	6	1
β-strand	83-88	6	1
α-helix	95-101	7
β-strand	104-105	2	2
α-helix	109-115	7
α-helix	133-138	6
β-strand	140-148	9	1
β-strand	155-159	5	1
β-strand	166-168	3	1
β-strand	178-185	8	1
α-helix	190-192	3
α-helix	195-204	10
α-helix	212	1
β-strand	213-218	6	1
β-strand	276-279	4	1
α-helix	298-308	11
β-strand	317-323	7	11
β-strand	329-335	7	11
α-helix	346-348	3
β-strand	353-357	5	11
β-strand	360-363	4	11
α-helix	372-374	3
β-strand	378-383	6	11
α-helix	387	1
β-strand	388	1	12
α-helix	389	1
β-strand	395	1	12
α-helix	398-400	3
α-helix	401-419	19
α-helix	423-443	21
α-helix	448-452	5
β-strand	456-457	2	13
β-strand	458-459	2	14
β-strand	467-468	2	13
α-helix	469-474	6
β-strand	482-487	6	14
α-helix	491-495	5
α-helix	501-505	5
β-strand	510-513	4	14
α-helix	517-524	8
β-strand	528	1	15
β-strand	531	1	15
β-strand	532-535	4	14
β-strand	538	1	16
α-helix	547-570	24
β-strand	577-580	4	17
β-strand	589-592	4	17
β-strand	593	1	16
α-helix	600-607	8
β-strand	625-628	4	17
α-helix	633-644	12
α-helix	649-665	17
α-helix	673-688	16

Chain CP1: 9 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	433-436	4
α-helix	442-461	20
α-helix	471-473	3
β-strand	475-477	3	18
β-strand	481-483	3	18
α-helix	514-518	5
α-helix	527-543	17
α-helix	554-563	10
α-helix	573-574	2
α-helix	580-588	9
α-helix	599-611	13

Chain DP1: 13 helices, 3 β-strands

Element	Residues	Length	Sheet
β-strand	10	1	19
α-helix	25-73	49
α-helix	78-111	34
α-helix	113	1
β-strand	114	1	19
α-helix	116-119	4
β-strand	120-129	10	6
α-helix	142-154	13
α-helix	156-163	8
α-helix	168-177	10
α-helix	179-181	3
α-helix	184-199	16
α-helix	203-226	24
α-helix	230-232	3
α-helix	235-242	8
α-helix	246-273	28

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Heat shock protein HSP 90-beta	AP1, BP1	protein	732	Homo sapiens	P08238 (AlphaFold model)
RAF proto-oncogene serine/threonine-protein kinase	CP1	protein	659	Homo sapiens	P04049 (AlphaFold model)
Hsp90 co-chaperone Cdc37	DP1	protein	394	Homo sapiens	Q16543 (AlphaFold model)

Sequence of entity 1 (AP1, BP1), FASTA

>7Z37_1 Heat shock protein HSP 90-beta (chains AP1, BP1)
MYPYDVPDYAEEVHHGEEEVETFAFQAEIAQLMSLIINTFYSNKEIFLRELISNASDALD
KIRYESLTDPSKLDSGKELKIDIIPNPQERTLTLVDTGIGMTKADLINNLGTIAKSGTKA
FMEALQAGADISMIGQFGVGFYSAYLVAEKVVVITKHNDDEQYAWESSAGGSFTVRADHG
EPIGRGTKVILHLKEDQTEYLEERRVKEVVKKHSQFIGYPITLYLEKEREKEISDDEAEE
EKGEKEEEDKDDEEKPKIEDVGSDEEDDSGKDKKKKTKKIKEKYIDQEELNKTKPIWTRN
PDDITQEEYGEFYKSLTNDWEDHLAVKHFSVEGQLEFRALLFIPRRAPFDLFENKKKKNN
IKLYVRRVFIMDSCDELIPEYLNFIRGVVDSEDLPLNISREMLQQSKILKVIRKNIVKKC
LELFSELAEDKENYKKFYEAFSKNLKLGIHEDSTNRRRLSELLRYHTSQSGDEMTSLSEY
VSRMKETQKSIYYITGESKEQVANSAFVERVRKRGFEVVYMTEPIDEYCVQQLKEFDGKS
LVSVTKEGLELPEDEEEKKKMEESKAKFENLCKLMKEILDKKVEKVTISNRLVSSPCCIV
TSTYGWTANMERIMKAQALRDNSTMGYMMAKKHLEINPDHPIVETLRQKAEADKNDKAVK
DLVVLLFETALLSSGFSLEDPQTHSNRIYRMIKLGLGIDEDEVAAEEPNAAVPDEIPPLE
GDEDASRMEEVD

Sequence of entity 2 (CP1), FASTA

>7Z37_2 RAF proto-oncogene serine/threonine-protein kinase (chains CP1)
MEHIQGAWKTISNGFGFKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDPSKTSNTIRV
FLPNKQRTVVNVRNGMSLHDCLMKALKVRGLQPECCAVFRLLHEHKGKKARLDWNTDAAS
LIGEELQVDFLDHVPLTTHNFARKTFLKLAFCDICQKFLLNGFRCQTCGYKFHEHCSTKV
PTMCVDWSNIRQLLLFPNSTIGDSGVPALPSLTMRRMRESVSRMPVSSQHRYSTPHAFTF
NTSSPSSEGSLSQRQRSTSTPNVHMVSTTLPVDSRMIEDAIRSHSESASPSALSSSPNNL
SPTGWSQPKTPVPAQRERAPVSGTQEKNKIRPRGQRDSSYYWEIEASEVMLSTRIGSGSF
GTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAVI
TQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGL
TVKIGDFGLATVKSRWSGSQQVEQPTGSVLWMAPEVIRMQDNNPFSFQSDVYSYGIVLYE
LMTGELPYSHINNRDQIIFMVGRGYASPDLSKLYKNCPKAMKRLVADCVKKVKEERPLFP
QILSSIELLQHSLPKINRSASEPSLHRAAHTEDINACTLTTSPRLPVFGSAWSHPQFEK

Sequence of entity 3 (DP1), FASTA

>7Z37_3 Hsp90 co-chaperone Cdc37 (chains DP1)
MVDYSVWDHIEVSDDEDETHPNIDTASLFRWRHQARVERMEQFQKEKEELDRGCRECKRK
VAECQRKLKELEVAEGGKAELERLQAEAQQLRKEERSWEQKLEEMRKKEKSMPWNVDTLS
KDGFSKSMVNTKPEKTEEDSEEVREQKHKTFVEKYEKQIKHFGMLRRWDDSQKYLSDNVH
LVCEETANYLVIWCIDLEVEEKCALMEQVAHQTIVMQFILELAKSLKVDPRACFRQFFTK
IKTADRQYMEGFNDELEAFKERVRGRAKLRIEKAMKEYEEEERKKRLGPGGLDPVEVYES
LPEELQKCFDVKDVQMLQDAISKMDPTDAKYHMQRCIDSGLWVPNSKASEAKEGEEAGPG
DPLLEAVPKTGDEKDVSVTRTRPLEQKLISEEDL

Ligands and cofactors

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

Primary citation

Structure of the RAF1-HSP90-CDC37 complex reveals the basis of RAF1 regulation. Garcia-Alonso, S., Mesa, P., Ovejero, L.P. et al. Mol Cell (2022) 82:3438-3452.e8. DOI 10.1016/j.molcel.2022.08.012 · 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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