ODPX_CHATD
ID ODPX_CHATD Reviewed; 442 AA.
AC G0S5Q0;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Pyruvate dehydrogenase complex protein X component, mitochondrial {ECO:0000303|PubMed:33567276};
DE AltName: Full=Dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex {ECO:0000303|PubMed:33567276};
DE AltName: Full=E3-binding protein {ECO:0000303|PubMed:33567276};
DE AltName: Full=Pyruvate dehydrogenase complex component E3BP {ECO:0000303|PubMed:33567276};
DE Flags: Precursor;
GN ORFNames=CTHT_0025050;
OS Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=759272;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=DSM 1495 / CBS 144.50 / IMI 039719;
RX PubMed=21784248; DOI=10.1016/j.cell.2011.06.039;
RA Amlacher S., Sarges P., Flemming D., van Noort V., Kunze R., Devos D.P.,
RA Arumugam M., Bork P., Hurt E.;
RT "Insight into structure and assembly of the nuclear pore complex by
RT utilizing the genome of a eukaryotic thermophile.";
RL Cell 146:277-289(2011).
RN [2]
RP FUNCTION, AND SUBUNIT.
RX PubMed=33567276; DOI=10.1016/j.celrep.2021.108727;
RA Kyrilis F.L., Semchonok D.A., Skalidis I., Tueting C., Hamdi F.,
RA O'Reilly F.J., Rappsilber J., Kastritis P.L.;
RT "Integrative structure of a 10-megadalton eukaryotic pyruvate dehydrogenase
RT complex from native cell extracts.";
RL Cell Rep. 34:108727-108727(2021).
RN [3]
RP FUNCTION, SUBUNIT, AND DOMAIN.
RX PubMed=34836937; DOI=10.1038/s41467-021-27287-4;
RA Tueting C., Kyrilis F.L., Mueller J., Sorokina M., Skalidis I., Hamdi F.,
RA Sadian Y., Kastritis P.L.;
RT "Cryo-EM snapshots of a native lysate provide structural insights into a
RT metabolon-embedded transacetylase reaction.";
RL Nat. Commun. 12:6933-6933(2021).
CC -!- FUNCTION: The 10-megadalton pyruvate dehydrogenase complex contains
CC multiple copies of three enzymatic components: pyruvate dehydrogenase
CC (E1), dihydrolipoamide acetyltransferase (E2) and lipoamide
CC dehydrogenase (E3) and catalyzes the overall oxidative decarboxylation
CC of pyruvate to form acetyl-CoA and CO(2) (PubMed:33567276,
CC PubMed:34836937). E3BP is responsible for tethering E3 in proximity to
CC the core, forming the entire metabolon, and the number of E3s is
CC limited by the number of E3BPs (PubMed:34836937). Within the complex,
CC pyruvate and thiamine pyrophosphate (TPP or vitamin B1) are bound by
CC pyruvate dehydrogenase E1 subunits alpha and beta and pyruvate is
CC decarboxylated leading to the 2-carbon hydrohyethyl bound to TPP. The
CC E2 component contains covalently-bound lipoyl cofactors and transfers
CC the hydroxyethyl group from TPP to an oxidized form of covalently bound
CC lipoamide, and the resulting acetyl group is then transferred to free
CC coenzyme A to form acetyl-CoA and reduced dihydrolipoamide-E2. Finally,
CC the flavoprotein dihydrolipoamide dehydrogenase (E3) re-oxidizes the
CC lipoyl group of dihydrolipoamide-E2 to form lipoamide-E2 and NADH. A
CC fourth subunit, E3BP, is responsible for tethering E3 in proximity to
CC the core, forming the entire metabolon (Probable).
CC {ECO:0000269|PubMed:33567276, ECO:0000269|PubMed:34836937,
CC ECO:0000305|PubMed:33567276}.
CC -!- SUBUNIT: Eukaryotic pyruvate dehydrogenase (PDH) complexes are
CC organized as a core consisting of the oligomeric dihydrolipoamide
CC acetyl-transferase (E2), around which are arranged multiple copies of
CC pyruvate dehydrogenase (E1), dihydrolipoamide dehydrogenase (E3) and
CC protein X (E3BP) bound by non-covalent bonds (PubMed:33567276). The
CC Chaetomium thermophilum PDH complex contains 60 E2 units, 12 E3BP
CC units, about 20 E1 units, and 12 or more E3 units (PubMed:33567276).
CC The units are organized in 1 E2 60-mer, 4 E3BP trimers, about 20 E1
CC tetramers, and a maximum of 12 E3 dimers (PubMed:33567276). The E3BP
CC trimers are bound inside the icosahedral core with tetrahedral symmetry
CC (PubMed:33567276). {ECO:0000269|PubMed:33567276}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255}.
CC -!- DOMAIN: The sequence organization of E3BP is highly similar to E2,
CC having an N-terminal lipoyl-binding domain (LD), a central peripheral
CC subunit binding domain (PSBD), and the C-terminal core region connected
CC by disordered linkers. {ECO:0000269|PubMed:34836937}.
CC -!- DOMAIN: E3BP is bound in a tripod-like manner and the interaction to
CC the E2 core is primarily mediated by a loop region of E3BP (residues
CC Pro-317 to Leu-336). {ECO:0000269|PubMed:34836937}.
CC -!- SIMILARITY: Belongs to the 2-oxoacid dehydrogenase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; GL988041; EGS20669.1; -; Genomic_DNA.
DR RefSeq; XP_006692965.1; XM_006692902.1.
DR STRING; 759272.G0S5Q0; -.
DR EnsemblFungi; EGS20669; EGS20669; CTHT_0025050.
DR GeneID; 18256543; -.
DR KEGG; cthr:CTHT_0025050; -.
DR eggNOG; KOG0557; Eukaryota.
DR HOGENOM; CLU_035825_2_0_1; -.
DR OrthoDB; 747232at2759; -.
DR Proteomes; UP000008066; Unassembled WGS sequence.
DR GO; GO:0045254; C:pyruvate dehydrogenase complex; IEA:InterPro.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0006086; P:acetyl-CoA biosynthetic process from pyruvate; IEA:InterPro.
DR Gene3D; 4.10.320.10; -; 1.
DR InterPro; IPR003016; 2-oxoA_DH_lipoyl-BS.
DR InterPro; IPR000089; Biotin_lipoyl.
DR InterPro; IPR045257; E2/Pdx1.
DR InterPro; IPR036625; E3-bd_dom_sf.
DR InterPro; IPR004167; PSBD.
DR InterPro; IPR011053; Single_hybrid_motif.
DR PANTHER; PTHR23151; PTHR23151; 1.
DR Pfam; PF00364; Biotin_lipoyl; 1.
DR Pfam; PF02817; E3_binding; 1.
DR SUPFAM; SSF47005; SSF47005; 1.
DR SUPFAM; SSF51230; SSF51230; 1.
DR PROSITE; PS50968; BIOTINYL_LIPOYL; 1.
DR PROSITE; PS00189; LIPOYL; 1.
DR PROSITE; PS51826; PSBD; 1.
PE 1: Evidence at protein level;
KW Lipoyl; Mitochondrion; Pyruvate; Reference proteome; Transit peptide.
FT TRANSIT 1..35
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 36..442
FT /note="Pyruvate dehydrogenase complex protein X component,
FT mitochondrial"
FT /evidence="ECO:0000255"
FT /id="PRO_0000456223"
FT DOMAIN 37..113
FT /note="Lipoyl-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
FT DOMAIN 175..215
FT /note="Peripheral subunit-binding (PSBD)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01170"
FT REGION 317..336
FT /note="Interaction to the E2 core"
FT /evidence="ECO:0000269|PubMed:34836937"
FT SITE 330
FT /note="E2-binding in a hydrophobic pocket in the E2 core"
FT /evidence="ECO:0000269|PubMed:34836937"
FT MOD_RES 78
FT /note="N6-lipoyllysine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01066"
SQ SEQUENCE 442 AA; 46832 MW; 016F90B1862273F2 CRC64;
MASLAAACRV SARLAARKLQ HDAAVRGFRS SAAALAAQNF MMPALSPTMT EGNIASWRVK
EGERFSAGDV LLEIETDKAT MDVEAQEDGI LMKIIQPDGS KGVQVGTRIA VVAEEGDDIT
KLEIPPDEGP QQLKAAAPAP APTPAPAPAS PQPQFAAPTP SPPKASTKVP ARKYPLLPSV
HQLIKENGLD ESAVSNITPT GPGGRILKGD VLAYLGKINP NTPAQISARF EKASHLDLSN
VKVAKPVEPE KPQEEKASAP APAPRAPEPP AKAVVSLPIS LSAVLEAQQR INKKLGIFLP
LSTFISRATE LANEELPLPT NYQPTADELF DQVLGLDKVP GYVSAAKQRA TRGNYVPDIK
APIPPKAAPK PKQKKIDIID ILAAAPKAKS VKPAGPSLVP GAVTEGLNVF SLQVPKTEER
RAKVFLERVK HVLENEPGRL VL
