7ZR5

CryoEM structure of HSP90-CDC37-BRAF(V600E)-PP5(closed) complex

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0001890	biological_process	placenta development
A	0003723	molecular_function	RNA binding
A	0003725	molecular_function	double-stranded RNA binding
A	0005515	molecular_function	protein binding
A	0005524	molecular_function	ATP binding
A	0005576	cellular_component	extracellular region
A	0005634	cellular_component	nucleus
A	0005654	cellular_component	nucleoplasm
A	0005737	cellular_component	cytoplasm
A	0005739	cellular_component	mitochondrion
A	0005829	cellular_component	cytosol
A	0005886	cellular_component	plasma membrane
A	0006457	biological_process	protein folding
A	0006986	biological_process	response to unfolded protein
A	0007004	biological_process	telomere maintenance via telomerase
A	0008180	cellular_component	COP9 signalosome
A	0009986	cellular_component	cell surface
A	0010033	biological_process	response to organic substance
A	0016020	cellular_component	membrane
A	0016887	molecular_function	ATP hydrolysis activity
A	0019062	biological_process	virion attachment to host cell
A	0019887	molecular_function	protein kinase regulator activity
A	0019900	molecular_function	kinase binding
A	0019901	molecular_function	protein kinase binding
A	0023026	molecular_function	MHC class II protein complex binding
A	0030235	molecular_function	nitric-oxide synthase regulator activity
A	0030511	biological_process	positive regulation of transforming growth factor beta receptor signaling pathway
A	0030911	molecular_function	TPR domain binding
A	0031072	molecular_function	heat shock protein binding
A	0031396	biological_process	regulation of protein ubiquitination
A	0031625	molecular_function	ubiquitin protein ligase binding
A	0032435	biological_process	negative regulation of proteasomal ubiquitin-dependent protein catabolic process
A	0032516	biological_process	positive regulation of phosphoprotein phosphatase activity
A	0032880	biological_process	regulation of protein localization
A	0032991	cellular_component	protein-containing complex
A	0034605	biological_process	cellular response to heat
A	0034751	cellular_component	aryl hydrocarbon receptor complex
A	0034774	cellular_component	secretory granule lumen
A	0042277	molecular_function	peptide binding
A	0042470	cellular_component	melanosome
A	0042802	molecular_function	identical protein binding
A	0042803	molecular_function	protein homodimerization activity
A	0042826	molecular_function	histone deacetylase binding
A	0043008	molecular_function	ATP-dependent protein binding
A	0043025	cellular_component	neuronal cell body
A	0043066	biological_process	negative regulation of apoptotic process
A	0044183	molecular_function	protein folding chaperone
A	0044294	cellular_component	dendritic growth cone
A	0044295	cellular_component	axonal growth cone
A	0045296	molecular_function	cadherin binding
A	0045429	biological_process	positive regulation of nitric oxide biosynthetic process
A	0045597	biological_process	positive regulation of cell differentiation
A	0046983	molecular_function	protein dimerization activity
A	0048156	molecular_function	tau protein binding
A	0048471	cellular_component	perinuclear region of cytoplasm
A	0050821	biological_process	protein stabilization
A	0051082	molecular_function	unfolded protein binding
A	0051131	biological_process	chaperone-mediated protein complex assembly
A	0051726	biological_process	regulation of cell cycle
A	0060255	biological_process	regulation of macromolecule metabolic process
A	0061077	biological_process	chaperone-mediated protein folding
A	0070062	cellular_component	extracellular exosome
A	0070182	molecular_function	DNA polymerase binding
A	0071353	biological_process	cellular response to interleukin-4
A	0097435	biological_process	supramolecular fiber organization
A	0097718	molecular_function	disordered domain specific binding
A	0101031	cellular_component	protein folding chaperone complex
A	0120293	cellular_component	dynein axonemal particle
A	0140662	molecular_function	ATP-dependent protein folding chaperone
A	0141069	molecular_function	receptor ligand inhibitor activity
A	1901799	biological_process	negative regulation of proteasomal protein catabolic process
A	1904813	cellular_component	ficolin-1-rich granule lumen
A	1905323	biological_process	telomerase holoenzyme complex assembly
A	1990226	molecular_function	histone methyltransferase binding
A	1990565	cellular_component	HSP90-CDC37 chaperone complex
A	2000010	biological_process	positive regulation of protein localization to cell surface
B	0001890	biological_process	placenta development
B	0003723	molecular_function	RNA binding
B	0003725	molecular_function	double-stranded RNA binding
B	0005515	molecular_function	protein binding
B	0005524	molecular_function	ATP binding
B	0005576	cellular_component	extracellular region
B	0005634	cellular_component	nucleus
B	0005654	cellular_component	nucleoplasm
B	0005737	cellular_component	cytoplasm
B	0005739	cellular_component	mitochondrion
B	0005829	cellular_component	cytosol
B	0005886	cellular_component	plasma membrane
B	0006457	biological_process	protein folding
B	0006986	biological_process	response to unfolded protein
B	0007004	biological_process	telomere maintenance via telomerase
B	0008180	cellular_component	COP9 signalosome
B	0009986	cellular_component	cell surface
B	0010033	biological_process	response to organic substance
B	0016020	cellular_component	membrane
B	0016887	molecular_function	ATP hydrolysis activity
B	0019062	biological_process	virion attachment to host cell
B	0019887	molecular_function	protein kinase regulator activity
B	0019900	molecular_function	kinase binding
B	0019901	molecular_function	protein kinase binding
B	0023026	molecular_function	MHC class II protein complex binding
B	0030235	molecular_function	nitric-oxide synthase regulator activity
B	0030511	biological_process	positive regulation of transforming growth factor beta receptor signaling pathway
B	0030911	molecular_function	TPR domain binding
B	0031072	molecular_function	heat shock protein binding
B	0031396	biological_process	regulation of protein ubiquitination
B	0031625	molecular_function	ubiquitin protein ligase binding
B	0032435	biological_process	negative regulation of proteasomal ubiquitin-dependent protein catabolic process
B	0032516	biological_process	positive regulation of phosphoprotein phosphatase activity
B	0032880	biological_process	regulation of protein localization
B	0032991	cellular_component	protein-containing complex
B	0034605	biological_process	cellular response to heat
B	0034751	cellular_component	aryl hydrocarbon receptor complex
B	0034774	cellular_component	secretory granule lumen
B	0042277	molecular_function	peptide binding
B	0042470	cellular_component	melanosome
B	0042802	molecular_function	identical protein binding
B	0042803	molecular_function	protein homodimerization activity
B	0042826	molecular_function	histone deacetylase binding
B	0043008	molecular_function	ATP-dependent protein binding
B	0043025	cellular_component	neuronal cell body
B	0043066	biological_process	negative regulation of apoptotic process
B	0044183	molecular_function	protein folding chaperone
B	0044294	cellular_component	dendritic growth cone
B	0044295	cellular_component	axonal growth cone
B	0045296	molecular_function	cadherin binding
B	0045429	biological_process	positive regulation of nitric oxide biosynthetic process
B	0045597	biological_process	positive regulation of cell differentiation
B	0046983	molecular_function	protein dimerization activity
B	0048156	molecular_function	tau protein binding
B	0048471	cellular_component	perinuclear region of cytoplasm
B	0050821	biological_process	protein stabilization
B	0051082	molecular_function	unfolded protein binding
B	0051131	biological_process	chaperone-mediated protein complex assembly
B	0051726	biological_process	regulation of cell cycle
B	0060255	biological_process	regulation of macromolecule metabolic process
B	0061077	biological_process	chaperone-mediated protein folding
B	0070062	cellular_component	extracellular exosome
B	0070182	molecular_function	DNA polymerase binding
B	0071353	biological_process	cellular response to interleukin-4
B	0097435	biological_process	supramolecular fiber organization
B	0097718	molecular_function	disordered domain specific binding
B	0101031	cellular_component	protein folding chaperone complex
B	0120293	cellular_component	dynein axonemal particle
B	0140662	molecular_function	ATP-dependent protein folding chaperone
B	0141069	molecular_function	receptor ligand inhibitor activity
B	1901799	biological_process	negative regulation of proteasomal protein catabolic process
B	1904813	cellular_component	ficolin-1-rich granule lumen
B	1905323	biological_process	telomerase holoenzyme complex assembly
B	1990226	molecular_function	histone methyltransferase binding
B	1990565	cellular_component	HSP90-CDC37 chaperone complex
B	2000010	biological_process	positive regulation of protein localization to cell surface
C	0000079	biological_process	regulation of cyclin-dependent protein serine/threonine kinase activity
C	0005515	molecular_function	protein binding
C	0005737	cellular_component	cytoplasm
C	0005829	cellular_component	cytosol
C	0006457	biological_process	protein folding
C	0006605	biological_process	protein targeting
C	0010608	biological_process	post-transcriptional regulation of gene expression
C	0019887	molecular_function	protein kinase regulator activity
C	0019900	molecular_function	kinase binding
C	0019901	molecular_function	protein kinase binding
C	0031072	molecular_function	heat shock protein binding
C	0050821	biological_process	protein stabilization
C	0051082	molecular_function	unfolded protein binding
C	0051087	molecular_function	protein-folding chaperone binding
C	0051879	molecular_function	Hsp90 protein binding
C	0060334	biological_process	regulation of type II interferon-mediated signaling pathway
C	0060338	biological_process	regulation of type I interferon-mediated signaling pathway
C	0070062	cellular_component	extracellular exosome
C	0097110	molecular_function	scaffold protein binding
C	0098779	biological_process	positive regulation of mitophagy in response to mitochondrial depolarization
C	0101031	cellular_component	protein folding chaperone complex
C	1990565	cellular_component	HSP90-CDC37 chaperone complex
K	0000165	biological_process	MAPK cascade
K	0001934	biological_process	positive regulation of protein phosphorylation
K	0002318	biological_process	myeloid progenitor cell differentiation
K	0004672	molecular_function	protein kinase activity
K	0004674	molecular_function	protein serine/threonine kinase activity
K	0004708	molecular_function	MAP kinase kinase activity
K	0004709	molecular_function	MAP kinase kinase kinase activity
K	0005509	molecular_function	calcium ion binding
K	0005515	molecular_function	protein binding
K	0005524	molecular_function	ATP binding
K	0005634	cellular_component	nucleus
K	0005737	cellular_component	cytoplasm
K	0005739	cellular_component	mitochondrion
K	0005829	cellular_component	cytosol
K	0005886	cellular_component	plasma membrane
K	0006468	biological_process	protein phosphorylation
K	0007165	biological_process	signal transduction
K	0007173	biological_process	epidermal growth factor receptor signaling pathway
K	0008542	biological_process	visual learning
K	0009887	biological_process	animal organ morphogenesis
K	0010628	biological_process	positive regulation of gene expression
K	0010764	biological_process	negative regulation of fibroblast migration
K	0010828	biological_process	positive regulation of glucose transmembrane transport
K	0016079	biological_process	synaptic vesicle exocytosis
K	0030154	biological_process	cell differentiation
K	0030878	biological_process	thyroid gland development
K	0031267	molecular_function	small GTPase binding
K	0031434	molecular_function	mitogen-activated protein kinase kinase binding
K	0033077	biological_process	T cell differentiation in thymus
K	0033138	biological_process	positive regulation of peptidyl-serine phosphorylation
K	0034446	biological_process	substrate adhesion-dependent cell spreading
K	0035019	biological_process	somatic stem cell population maintenance
K	0036211	biological_process	protein modification process
K	0042127	biological_process	regulation of cell population proliferation
K	0042802	molecular_function	identical protein binding
K	0043005	cellular_component	neuron projection
K	0043066	biological_process	negative regulation of apoptotic process
K	0043149	biological_process	stress fiber assembly
K	0043231	cellular_component	intracellular membrane-bounded organelle
K	0043367	biological_process	CD4-positive, alpha-beta T cell differentiation
K	0043368	biological_process	positive T cell selection
K	0043369	biological_process	CD4-positive or CD8-positive, alpha-beta T cell lineage commitment
K	0043434	biological_process	response to peptide hormone
K	0043524	biological_process	negative regulation of neuron apoptotic process
K	0044297	cellular_component	cell body
K	0044877	molecular_function	protein-containing complex binding
K	0045580	biological_process	regulation of T cell differentiation
K	0046632	biological_process	alpha-beta T cell differentiation
K	0046872	molecular_function	metal ion binding
K	0048538	biological_process	thymus development
K	0048679	biological_process	regulation of axon regeneration
K	0048680	biological_process	positive regulation of axon regeneration
K	0050772	biological_process	positive regulation of axonogenesis
K	0050852	biological_process	T cell receptor signaling pathway
K	0051496	biological_process	positive regulation of stress fiber assembly
K	0051591	biological_process	response to cAMP
K	0060291	biological_process	long-term synaptic potentiation
K	0060323	biological_process	head morphogenesis
K	0060324	biological_process	face development
K	0070371	biological_process	ERK1 and ERK2 cascade
K	0070374	biological_process	positive regulation of ERK1 and ERK2 cascade
K	0071277	biological_process	cellular response to calcium ion
K	0071466	biological_process	cellular response to xenobiotic stimulus
K	0072577	biological_process	endothelial cell apoptotic process
K	0090150	biological_process	establishment of protein localization to membrane
K	0097110	molecular_function	scaffold protein binding
K	0098793	cellular_component	presynapse
K	0106310	molecular_function	protein serine kinase activity
K	1900026	biological_process	positive regulation of substrate adhesion-dependent cell spreading
K	1902531	biological_process	regulation of intracellular signal transduction
K	1990090	biological_process	cellular response to nerve growth factor stimulus
K	2000301	biological_process	negative regulation of synaptic vesicle exocytosis
K	2000352	biological_process	negative regulation of endothelial cell apoptotic process
P	0000165	biological_process	MAPK cascade
P	0000278	biological_process	mitotic cell cycle
P	0003723	molecular_function	RNA binding
P	0004721	molecular_function	phosphoprotein phosphatase activity
P	0004722	molecular_function	protein serine/threonine phosphatase activity
P	0005515	molecular_function	protein binding
P	0005524	molecular_function	ATP binding
P	0005634	cellular_component	nucleus
P	0005654	cellular_component	nucleoplasm
P	0005737	cellular_component	cytoplasm
P	0005829	cellular_component	cytosol
P	0005886	cellular_component	plasma membrane
P	0006281	biological_process	DNA repair
P	0006302	biological_process	double-strand break repair
P	0006351	biological_process	DNA-templated transcription
P	0006470	biological_process	protein dephosphorylation
P	0008289	molecular_function	lipid binding
P	0010288	biological_process	response to lead ion
P	0016787	molecular_function	hydrolase activity
P	0016791	molecular_function	phosphatase activity
P	0017018	molecular_function	myosin phosphatase activity
P	0032991	cellular_component	protein-containing complex
P	0035970	biological_process	peptidyl-threonine dephosphorylation
P	0042802	molecular_function	identical protein binding
P	0043123	biological_process	positive regulation of canonical NF-kappaB signal transduction
P	0043231	cellular_component	intracellular membrane-bounded organelle
P	0043278	biological_process	response to morphine
P	0043531	molecular_function	ADP binding
P	0046872	molecular_function	metal ion binding
P	0048156	molecular_function	tau protein binding
P	0051879	molecular_function	Hsp90 protein binding
P	0070262	biological_process	peptidyl-serine dephosphorylation
P	0101031	cellular_component	protein folding chaperone complex
P	1904550	biological_process	response to arachidonic acid

Functional Information from PROSITE/UniProt

site_id	PS00107
Number of Residues	21
Details	PROTEIN_KINASE_ATP Protein kinases ATP-binding region signature. IGSGSFGTVYkGkwhgd.............VAVK

Chain	Residue	Details
K	ILE463-LYS483

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site_id	PS00108
Number of Residues	13
Details	PROTEIN_KINASE_ST Serine/Threonine protein kinases active-site signature. IiHrDLKsnNIFL

Chain	Residue	Details
K	ILE572-LEU584

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site_id	PS00479
Number of Residues	46
Details	ZF_DAG_PE_1 Zinc finger phorbol-ester/DAG-type signature. HnFvrktfftlaf.CdfCrklLfqgfr.....CqtCgykfHqrCstevplm..C

Chain	Residue	Details
K	HIS235-CYS280

---

site_id	PS00125
Number of Residues	6
Details	SER_THR_PHOSPHATASE Serine/threonine specific protein phosphatases signature. LRGNHE

Chain	Residue	Details
P	LEU300-GLU305

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site_id	PS00298
Number of Residues	10
Details	HSP90 Heat shock hsp90 proteins family signature. YsNKEIFLRE

Chain	Residue	Details
A	TYR33-GLU42

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Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	1
Details	ACT_SITE: Proton donor/acceptor => ECO:0000269|PubMed:15155720

Chain	Residue	Details
P	HIS304
A	LYS107
A	PHE133
A	ARG392
B	ASN46
B	LYS107
B	PHE133
B	ARG392

---

site_id	SWS_FT_FI2
Number of Residues	4
Details	BINDING: BINDING => ECO:0000269|PubMed:15155720, ECO:0000269|PubMed:15577939, ECO:0000269|PubMed:19601647, ECO:0007744|PDB:1S95, ECO:0007744|PDB:1WAO, ECO:0007744|PDB:3H60, ECO:0007744|PDB:3H61, ECO:0007744|PDB:3H62, ECO:0007744|PDB:3H63, ECO:0007744|PDB:3H64

Chain	Residue	Details
P	ASP242
P	ASP271
P	ASN303
P	HIS352

---

site_id	SWS_FT_FI3
Number of Residues	4
Details	BINDING: BINDING => ECO:0000269|PubMed:15155720

Chain	Residue	Details
P	HIS244
P	ARG275
P	ARG400
P	HIS427
K	CYS264
K	HIS269
K	CYS272
K	CYS280

---

site_id	SWS_FT_FI4
Number of Residues	2
Details	BINDING: BINDING => ECO:0000255|PROSITE-ProRule:PRU00159

Chain	Residue	Details
K	ILE463
K	LYS483
B	LYS219
B	LYS577

---

site_id	SWS_FT_FI5
Number of Residues	2
Details	SITE: Breakpoint for translocation to form KIAA1549-BRAF fusion protein

Chain	Residue	Details
K	ASP380
K	MET438

---

site_id	SWS_FT_FI6
Number of Residues	1
Details	MOD_RES: N-acetylalanine => ECO:0000269|Ref.8

Chain	Residue	Details
K	ALA2
B	SER255

---

site_id	SWS_FT_FI7
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569

Chain	Residue	Details
K	SER151
B	SER261

---

site_id	SWS_FT_FI8
Number of Residues	2
Details	MOD_RES: Phosphoserine => ECO:0000250|UniProtKB:P28028

Chain	Residue	Details
K	SER333
K	SER750

---

site_id	SWS_FT_FI9
Number of Residues	1
Details	MOD_RES: Phosphoserine; by SGK1 => ECO:0000269|PubMed:11410590, ECO:0000269|Ref.8, ECO:0007744|PubMed:23186163

Chain	Residue	Details
K	SER365
B	TYR301

---

site_id	SWS_FT_FI10
Number of Residues	1
Details	MOD_RES: Phosphothreonine; by autocatalysis => ECO:0000269|PubMed:1508179

Chain	Residue	Details
K	THR373
A	TYR484
B	TYR305
B	TYR484

---

site_id	SWS_FT_FI11
Number of Residues	1
Details	MOD_RES: Phosphothreonine => ECO:0000269|Ref.8

Chain	Residue	Details
K	THR396
B	SER307

---

site_id	SWS_FT_FI12
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0000269|Ref.8

Chain	Residue	Details
K	SER399
B	LYS399

---

site_id	SWS_FT_FI13
Number of Residues	1
Details	MOD_RES: Phosphothreonine => ECO:0000269|Ref.8, ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163

Chain	Residue	Details
K	THR401
A	LYS481
B	LYS435
B	LYS481

---

site_id	SWS_FT_FI14
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163

Chain	Residue	Details
K	SER446
B	SER445

---

site_id	SWS_FT_FI15
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:18669648

Chain	Residue	Details
K	SER447
B	THR479

---

site_id	SWS_FT_FI16
Number of Residues	1
Details	MOD_RES: Omega-N-methylarginine; by PRMT5 => ECO:0000269|PubMed:21917714

Chain	Residue	Details
K	ARG671
B	LYS531

---

site_id	SWS_FT_FI17
Number of Residues	1
Details	MOD_RES: Phosphoserine => ECO:0000269|Ref.8, ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163

Chain	Residue	Details
K	SER729
B	LYS574

---

site_id	SWS_FT_FI18
Number of Residues	1
Details	MOD_RES: Phosphothreonine; by MAPK1 => ECO:0000269|PubMed:19710016

Chain	Residue	Details
K	THR753
B	CYS590

---

site_id	SWS_FT_FI19
Number of Residues	2
Details	CROSSLNK: Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) => ECO:0000269|PubMed:23907581

Chain	Residue	Details
K	LYS578
B	LYS624

---

site_id	SWS_FT_FI20
Number of Residues	2
Details	MOD_RES: Phosphoserine => ECO:0007744|PubMed:24275569

Chain	Residue	Details
A	SER669
B	SER669

---

site_id	SWS_FT_FI21
Number of Residues	2
Details	MOD_RES: Phosphoserine; by PLK2 and PLK3 => ECO:0000269|PubMed:22828320

Chain	Residue	Details
A	SER718
B	SER718

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site_id	SWS_FT_FI22
Number of Residues	4
Details	CARBOHYD: O-linked (GlcNAc) serine => ECO:0000250

Chain	Residue	Details
A	SER434
A	SER452
B	SER434
B	SER452

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Catalytic Information from CSA

site_id	MCSA1
Number of Residues	10
Details	M-CSA 472

Chain	Residue	Details
P	ASP242	metal ligand
P	HIS244	metal ligand
P	ASP271	metal ligand
P	ASP274	activator, proton donor
P	ARG275	transition state stabiliser
P	ASN303	metal ligand, transition state stabiliser
P	HIS304	proton acceptor, proton donor, proton relay
P	HIS352	metal ligand
P	ARG400	transition state stabiliser
P	HIS427	activator, metal ligand

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