9MHH: PI3KC3-C1

PI3KC3-C1 in complex with RAB1A. VPS34 kinase domain active conformation. Determined by electron microscopy at 4.5 Å resolution. Released 12 Feb 2025.

Method: Electron microscopy
Resolution: 4.5 Å
Organism: Homo sapiens
Chains: 5
Atoms: 11,243
Mol. weight: 394.13 kDa
Ligands: GTP, MG
Released: 12 Feb 2025

Explore 9MHH in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9MHH contains 143 α-helices and 102 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: 72 helices, 49 β-strands

Element	Residues	Length	Sheet
α-helix	17-22	6
β-strand	26-34	9	1
β-strand	39-45	7	1
β-strand	48-56	9	1
α-helix	64-78	15
β-strand	84	1	2
β-strand	89-95	7	1
β-strand	98-104	7	1
β-strand	108-109	2	2
α-helix	110-113	4
α-helix	119-121	3
α-helix	122-141	20
β-strand	154-156	3	2
β-strand	162-164	3	2
β-strand	175-176	2	3
α-helix	180-183	4
β-strand	194	1	4
α-helix	199-201	3
β-strand	202-203	2	3
α-helix	205-208	4
α-helix	230-232	3
α-helix	233-236	4
α-helix	237-252	16
β-strand	260	1	4
α-helix	261-269	9
α-helix	275-279	5
α-helix	284-293	10
α-helix	298-300	3
α-helix	304-311	8
β-strand	312	1	5
β-strand	316	1	5
α-helix	318-319	2
α-helix	320-324	5
α-helix	325-329	5
α-helix	330-332	3
α-helix	336-338	3
α-helix	339-358	20
α-helix	372-383	12
α-helix	386-388	3
α-helix	392-405	14
α-helix	406-408	3
α-helix	411-413	3
α-helix	414-418	5
α-helix	419-425	7
α-helix	431-446	16
α-helix	453-455	3
α-helix	458	1
α-helix	459-463	5
α-helix	464-467	4
α-helix	468-472	5
α-helix	476-509	34
α-helix	526-544	19
α-helix	550-568	19
α-helix	570-572	3
α-helix	573-578	6
α-helix	579-581	3
α-helix	582-586	5
α-helix	591-608	18
α-helix	610-612	3
α-helix	613-623	11
α-helix	629-644	16
α-helix	650-660	11
α-helix	661-665	5
α-helix	669-685	17
α-helix	688-690	3
α-helix	691-695	5
α-helix	696-699	4
β-strand	703	1	6
α-helix	713-719	7
β-strand	720	1	6
α-helix	721-725	5
α-helix	726-733	8
α-helix	738-752	15
α-helix	759-762	4
α-helix	765-776	12
α-helix	781-789	9
α-helix	791-807	17
β-strand	818-820	3	7
α-helix	821-824	4
β-strand	829-832	4	7
α-helix	939-966	28
α-helix	974-976	3
β-strand	985-989	5	8
β-strand	996-1001	6	9
β-strand	1007-1012	6	9
β-strand	1017-1021	5	9
α-helix	1022-1026	5
β-strand	1036-1038	3	9
β-strand	1045-1051	7	10
β-strand	1056-1061	6	10
β-strand	1065-1071	7	10
α-helix	1074-1075	2
α-helix	1079-1080	2
β-strand	1082-1089	8	10
β-strand	1098-1105	8	11
β-strand	1110-1116	7	11
β-strand	1120-1125	6	11
β-strand	1131-1136	6	11
α-helix	1139-1141	3
β-strand	1144-1149	6	12
β-strand	1155-1160	6	12
β-strand	1164-1169	6	12
β-strand	1174-1180	7	12
α-helix	1185-1186	2
β-strand	1187-1192	6	13
β-strand	1199-1204	6	13
β-strand	1210-1214	5	13
β-strand	1219-1225	7	13
α-helix	1230	1
β-strand	1242-1248	7	14
β-strand	1255-1260	6	14
β-strand	1265-1269	5	14
α-helix	1273-1275	3
β-strand	1277-1280	4	14
α-helix	1285-1287	3
β-strand	1288-1295	8	13
β-strand	1298-1305	8	13
α-helix	1322-1325	4
β-strand	1332-1339	8	8
β-strand	1343-1349	7	8
β-strand	1354-1357	4	8

Chain B: 47 helices, 28 β-strands

Element	Residues	Length	Sheet
β-strand	6-11	6	7
α-helix	12-14	3
β-strand	18-27	10	15
α-helix	29-34	6
α-helix	35-40	6
α-helix	42-46	5
α-helix	48-50	3
α-helix	54-55	2
β-strand	58-65	8	16
β-strand	68-69	2	16
β-strand	74-75	2	16
α-helix	76-78	3
β-strand	85-96	12	15
α-helix	97-99	3
β-strand	104-113	10	16
β-strand	119-128	10	16
β-strand	130	1	17
β-strand	135	1	7
β-strand	136	1	17
α-helix	137	1
β-strand	140-144	5	15
α-helix	145	1
β-strand	146-147	2	16
α-helix	150-152	3
β-strand	160	1	16
α-helix	171-183	13
α-helix	191-211	21
β-strand	216-221	6	15
β-strand	223-226	4	7
β-strand	229-234	6	7
α-helix	265-275	11
α-helix	290-300	11
α-helix	307-309	3
α-helix	310-318	9
α-helix	320-323	4
α-helix	330-336	7
α-helix	342-352	11
α-helix	356-359	4
α-helix	360-363	4
α-helix	364-367	4
α-helix	374-384	11
α-helix	389-401	13
α-helix	402-404	3
α-helix	408-412	5
α-helix	476-483	8
α-helix	487-502	16
α-helix	504-509	6
α-helix	511-529	19
α-helix	533-561	29
α-helix	566-578	13
β-strand	591-592	2	18
β-strand	600-611	12	18
α-helix	618	1
β-strand	619-625	7	18
β-strand	630-637	8	18
α-helix	642-660	19
β-strand	672-674	3	18
β-strand	679-683	5	18
β-strand	688-689	2	19
α-helix	690-697	8
α-helix	700-707	8
β-strand	709	1	20
α-helix	714-716	3
β-strand	717	1	20
α-helix	719-738	20
α-helix	746-748	3
β-strand	749-751	3	19
β-strand	757-759	3	19
α-helix	781-786	6
α-helix	793-811	19
α-helix	813-822	10
α-helix	829-833	5
α-helix	835-846	12
α-helix	852-867	16
α-helix	871-886	16

Chain C: 9 helices, 3 β-strands

Element	Residues	Length	Sheet
α-helix	57-61	5
α-helix	75-200	126
α-helix	201-205	5
β-strand	208-210	3	21
β-strand	260-263	4	21
β-strand	265-271	7	21
α-helix	277-284	8
α-helix	299-321	23
α-helix	332-335	4
α-helix	341-361	21
α-helix	374-381	8
α-helix	399-405	7

Chain D: 7 helices, 11 β-strands

Element	Residues	Length	Sheet
α-helix	139-171	33
α-helix	177-266	90
α-helix	269-273	5
β-strand	276-279	4	22
β-strand	282-285	4	22
β-strand	288-290	3	22
α-helix	300-321	22
β-strand	328-331	4	23
β-strand	333	1	24
β-strand	335	1	24
β-strand	338-341	4	23
β-strand	348-350	3	23
α-helix	356-359	4
α-helix	363-386	24
β-strand	395-397	3	25
β-strand	402-404	3	25
β-strand	412-414	3	25
α-helix	422-447	26

Chain E: 8 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	5	1	26
β-strand	8	1	26
β-strand	10-15	6	27
β-strand	16-17	2	28
α-helix	24-32	9
β-strand	48-55	8	27
β-strand	58-65	8	27
α-helix	71-73	3
α-helix	79-81	3
β-strand	86	1	29
β-strand	88-92	5	28
α-helix	96-100	5
α-helix	102-112	11
β-strand	118	1	29
β-strand	121-124	4	28
α-helix	129-131	3
α-helix	136-146	11
β-strand	150-152	3	28
α-helix	160-175	16

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Phosphoinositide 3-kinase regulatory subunit 4	A	protein	1409	Homo sapiens	Q99570 (AlphaFold model)
Phosphatidylinositol 3-kinase catalytic subunit type 3	B	protein	887	Homo sapiens	Q8NEB9 (AlphaFold model)
Beclin 1-associated autophagy-related key regulator	C	protein	492	Homo sapiens	Q6ZNE5 (AlphaFold model)
Beclin-1	D	protein	450	Homo sapiens	Q14457 (AlphaFold model)
Ras-related protein Rab-1A	E	protein	226	Homo sapiens	P62820

Sequence of entity 1 (A), FASTA

>9MHH_1 Phosphoinositide 3-kinase regulatory subunit 4 (chains A)
MGNQLAGIAPSQILSVESYFSDIHDFEYDKSLGSTRFFKVARAKHREGLVVVKVFAIQDP
TLPLTSYKQELEELKIRLNSAQNCLPFQKASEKASEKAAMLFRQYVRDNLYDRISTRPFL
NNIEKRWIAFQILTAVDQAHKSGVRHGDIKTENVMVTSWNWVLLTDFASFKPTYLPEDNP
ADFNYFFDTSRRRTCYIAPERFVDGGMFATELEYMRDPSTPLVDLNSNQRTRGELKRAMD
IFSAGCVIAELFTEGVPLFDLSQLLAYRNGHFFPEQVLNKIEDHSIRELVTQMIHREPDK
RLEAEDYLKQQRGNAFPEIFYTFLQPYMAQFAKETFLSADERILVIRKDLGNIIHNLCGH
DLPEKAEGEPKENGLVILVSVITSCLQTLKYCDSKLAALELILHLAPRLSVEILLDRITP
YLLHFSNDSVPRVRAEALRTLTKVLALVKEVPRNDINIYPEYILPGIAHLAQDDATIVRL
AYAENIALLAETALRFLELVQLKNLNMENDPNNEEIDEVTHPNGNYDTELQALHEMVQQK
VVTLLSDPENIVKQTLMENGITRLCVFFGRQKANDVLLSHMITFLNDKNDWHLRGAFFDS
IVGVAAYVGWQSSSILKPLLQQGLSDAEEFVIVKALYALTCMCQLGLLQKPHVYEFASDI
APFLCHPNLWIRYGAVGFITVVARQISTADVYCKLMPYLDPYITQPIIQIERKLVLLSVL
KEPVSRSIFDYALRSKDITSLFRHLHMRQKKRNGSLPDCPPPEDPAIAQLLKKLLSQGMT
EEEEDKLLALKDFMMKSNKAKANIVDQSHLHDSSQKGVIDLAALGITGRQVDLVKTKQEP
DDKRARKHVKQDSNVNEEWKSMFGSLDPPNMPQALPKGSDQEVIQTGKPPRSESSAGICV
PLSTSSQVPEVTTVQNKKPVIPVLSSTILPSTYQIRITTCKTELQQLIQQKREQCNAERI
AKQMMENAEWESKPPPPGWRPKGLLVAHLHEHKSAVNRIRVSDEHSLFATCSNDGTVKIW
NSQKMEGKTTTTRSILTYSRIGGRVKTLTFCQGSHYLAIASDNGAVQLLGIEASKLPKSP
KIHPLQSRILDQKEDGCVVDMHHFNSGAQSVLAYATVNGSLVGWDLRSSSNAWTLKHDLK
SGLITSFAVDIHQCWLCIGTSSGTMACWDMRFQLPISSHCHPSRARIRRLSMHPLYQSWV
IAAVQGNNEVSMWDMETGDRRFTLWASSAPPLSELQPSPHSVHGIYCSPADGNPILLTAG
SDMKIRFWDLAYPERSYVVAGSTSSPSVSYYRKIIEGTEVVQEIQNKQKVGPSDDTPRRG
PESLPVGHHDIITDVATFQTTQGFIVTASRDGIVKVWKGTENLYFQSGMAAWSHPQFEKG
GGARGGSGGGSWSHPQFEKGFDYKDDDDK

Sequence of entity 2 (B), FASTA

>9MHH_2 Phosphatidylinositol 3-kinase catalytic subunit type 3 (chains B)
MGEAEKFHYIYSCDLDINVQLKIGSLEGKREQKSYKAVLEDPMLKFSGLYQETCSDLYVT
CQVFAEGKPLALPVRTSYKAFSTRWNWNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKAV
PVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTKTPGRTSSTLSEDQMSRLAKLTK
AHRQGHMVKVDWLDRLTFREIEMINESEKRSSNFMYLMVEFRCVKCDDKEYGIVYYEKDG
DESSPILTSFELVKVPDPQMSMENLVESKHHKLARSLRSGPSDHDLKPNAATRDQLNIIV
SYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDV
EDSLELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKNGLEPTKK
DSQSSVSENVSNSGINSAEIDSSQIITSPLPSVSSPPPASKTKEVPDGENLEQDLCTFLI
SRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLNVMRRFSQALLKGDKSVRVMRS
LLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMNLSDVELIPLPLEPQVK
IRGIIPETATLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRK
ENLDLKLTPYKVLATSTKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSENGPNGISAE
VMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPMKLN
KEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEPDKTVK
KVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQYWRK

Sequence of entity 3 (C), FASTA

>9MHH_3 Beclin 1-associated autophagy-related key regulator (chains C)
MASPSGKGARALEAPGCGPRPLARDLVDSVDDAEGLYVAVERCPLCNTTRRRLTCAKCVQ
SGDFVYFDGRDRERFIDKKERLSRLKSKQEEFQKEVLKAMEGKWITDQLRWKIMSCKMRI
EQLKQTICKGNEEMEKNSEGLLKTKEKNQKLYSRAQRHQEKKEKIQRHNRKLGDLVEKKT
IDLRSHYERLANLRRSHILELTSVIFPIEEVKTGVRDPADVSSESDSAMTSSTVSKLAEA
RRTTYLSGRWVCDDHNGDTSISITGPWISLPNNGDYSAYYSWVEEKKTTQGPDMEQSNPA
YTISAALCYATQLVNILSHILDVNLPKKLCNSEFCGENLSKQKFTRAVKKLNANILYLCF
SQHVNLDQLQPLHTLRNLMYLVSPSSEHLGRSGPFEVRADLEESMEFVDPGVAGESDESG
DERVSDEETDLGTDWENLPSPRFCDIPSQSVEVSQSQSTQASPPIASSSAGGMISSAAAS
VTSWFKAYTGHR

Sequence of entity 4 (D), FASTA

>9MHH_4 Beclin-1 (chains D)
MEGSKTSNNSTMQVSFVCQRCSQPLKLDTSFKILDRVTIQELTAPLLTTAQAKPGETQEE
ETNSGEEPFIETPRQDGVSRRFIPPARMMSTESANSFTLIGEASDGGTMENLSRRLKVTG
DLFDIMSGQTDVDHPLCEECTDTLLDQLDTQLNVTENECQNYKRCLEILEQMNEDDSEQL
QMELKELALEEERLIQELEDVEKNRKIVAENLEKVQAEAERLDQEEAQYQREYSEFKRQQ
LELDDELKSVENQMRYAQTQLDKLKKTNVFNATFHIWHSGQFGTINNFRLGRLPSVPVEW
NEINAAWGQTVLLLHALANKMGLKFQRYRLVPYGNHSYLESLTDKSKELPLYCSGGLRFF
WDNKFDHAMVAFLDCVQQFKEEVEKGETRFCLPYRMDVEKGKIEDTGGSGGSYSIKTQFN
SEEQWTKALKFMLTNLKWGLAWVSSQFYNK

Sequence of entity 5 (E), FASTA

>9MHH_5 Ras-related protein Rab-1A (chains E)
MKSSHHHHHHENLYFQSNAMGMSSMNPEYDYLFKLLLIGDSGVGKSCLLLRFADDTYTES
YISTIGVDFKIRTIELDGKTIKLQIWDTAGLERFRTITSSYYRGAHGIIVVYDVTDQESF
NNVKQWLQEIDRYASENVNKLLVGNKCDLTTKKVVDYTTAKEFADSLGIPFLETSAKNAT
NVEQSFMTMAAEIKKRMGPGATAGGAEKSNVKIQSTPVKQSGGGCC

Ligands and cofactors

ID	Name	Formula	Copies
GTP	Guanosine-5'-triphosphate	C10 H16 N5 O14 P3	2
MG	Magnesium ion	Mg	2

Primary citation

Structural pathway for PI3-kinase regulation by VPS15 in autophagy. Cook, A.S.I., Chen, M., Nguyen, T.N. et al. Science (2025) 388:eadl3787-eadl3787. DOI 10.1126/science.adl3787 · PubMed

Other PDB entries of the same protein (UniProt Q99570 (AlphaFold model), which also has an AlphaFold model), best resolution first:

9MHF 2.73 Å, Cryo-EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L)
9RX5 3.15 Å, VPS34-CII (VPS34 199-REIE-202 to 199-AAAA-202 mutant) bound to RAB5A (Q79L)
9MHG 3.2 Å, Cryo EM reconstruction of PI3KC3-C1 in complex with Human RAB1A(Q70L), VPS34 kinase…
9RX7 3.33 Å, VPS34-CI bound to NRBF2 MIT domain (residues 1-79)
9RX6 3.52 Å, VPS34-CII (VPS34 199-REIE-202 to 199-ERIR-202 mutant) bound to RAB5A (Q79L) on the VPS15…
9TW2 3.58 Å, Cryo-EM structure of human VPS34-CI in complex with GABARAP
9TW3 3.6 Å, Cryo-EM structure of human VPS34-CI in complex with GABARAP - alternative conformation
9TZ3 3.66 Å, Cryo-EM structure of human VPS34-CI with ADP:MgF3
9RX4 3.67 Å, VPS34-CI bound to NRBF2 and RAB1A
13BV 3.77 Å, Cryo-EM structure of human PI3KC3-C1 complex
9RX8 3.87 Å, Apo VPS34-cii (VPS34/VPS15/BECLIN1/UVRAG)
9RX9 3.99 Å, VPS34-CII bound to RAB5A-GTP 1-212 (C19S, C63S, Q79L) on the VPS34 subunit

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