9MNW: Human MPC
Cryo-EM structure of human MPC in complex with GW604714. Determined by electron microscopy at 3.35 Å resolution. Released 5 Mar 2025.
- Method
- Electron microscopy
- Resolution
- 3.35 Å
- Organisms
- Homo sapiens, Mus musculus, synthetic construct
- Chains
- 6
- Atoms
- 4,870
- Mol. weight
- 159.98 kDa
- Ligands
- A1BM8
- Released
- 5 Mar 2025
Explore 9MNW in 3D
Show helices and sheets
RCSB PDB
PDBe
Secondary structure: helices and β-sheets
9MNW contains 16 α-helices and 39 β-strands across 6 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: 5 helices, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 13-18 | 6 | |
| α-helix | 20-23 | 4 | |
| α-helix | 25-43 | 19 | |
| α-helix | 53-71 | 19 | |
| α-helix | 79-110 | 32 | |
Chain B: 7 helices, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 11-23 | 13 | |
| α-helix | 26-28 | 3 | |
| α-helix | 29-32 | 4 | |
| α-helix | 41-60 | 20 | |
| α-helix | 64-66 | 3 | |
| α-helix | 69-87 | 19 | |
| α-helix | 95-123 | 29 | |
Chain C: 1 helix, 15 β-strands
| Element | Residues | Length | Sheet |
|---|
| β-strand | 3-4 | 2 | 7 |
| β-strand | 7 | 1 | 8 |
| β-strand | 10-13 | 4 | 9 |
| β-strand | 18-23 | 6 | 8 |
| β-strand | 24-25 | 2 | 7 |
| β-strand | 31 | 1 | 9 |
| β-strand | 34-39 | 6 | 9 |
| β-strand | 46-51 | 6 | 9 |
| β-strand | 57-59 | 3 | 9 |
| β-strand | 64 | 1 | 8 |
| β-strand | 67-72 | 6 | 8 |
| α-helix | 73-75 | 3 | |
| β-strand | 77-82 | 6 | 8 |
| β-strand | 91-99 | 9 | 9 |
| β-strand | 105-108 | 4 | 9 |
| β-strand | 113-117 | 5 | 9 |
Chain D: 1 helix, 11 β-strands
| Element | Residues | Length | Sheet |
|---|
| β-strand | 5-7 | 3 | 1 |
| β-strand | 11-12 | 2 | 2 |
| β-strand | 17-23 | 7 | 1 |
| β-strand | 33-39 | 7 | 3 |
| β-strand | 45-51 | 7 | 3 |
| β-strand | 58-60 | 3 | 3 |
| β-strand | 68-73 | 6 | 1 |
| α-helix | 74-76 | 3 | |
| β-strand | 78-84 | 7 | 1 |
| β-strand | 92-99 | 8 | 3 |
| β-strand | 117-119 | 3 | 3 |
| β-strand | 120-121 | 2 | 2 |
Chain E: 0 helices, 13 β-strands
| Element | Residues | Length | Sheet |
|---|
| β-strand | 5-6 | 2 | 4 |
| β-strand | 10-11 | 2 | 5 |
| β-strand | 19-24 | 6 | 4 |
| β-strand | 30-31 | 2 | 6 |
| β-strand | 36-37 | 2 | 6 |
| β-strand | 39-44 | 6 | 5 |
| β-strand | 51-55 | 5 | 5 |
| β-strand | 59-60 | 2 | 5 |
| β-strand | 68-73 | 6 | 4 |
| β-strand | 76-81 | 6 | 4 |
| β-strand | 91-96 | 6 | 5 |
| β-strand | 102-103 | 2 | 5 |
| β-strand | 107-109 | 3 | 5 |
Chain F: 2 helices, 0 β-strands
| Element | Residues | Length | Sheet |
|---|
| α-helix | 375-385 | 11 | |
| α-helix | 394-404 | 11 | |
Molecules and chains
| Molecule | Chains | Type | Length | Organism | UniProt |
|---|
| Mitochondrial pyruvate carrier 1 | A | protein | 115 | Homo sapiens | Q9Y5U8 (AlphaFold model) |
| Mitochondrial pyruvate carrier 2 | B | protein | 127 | Homo sapiens | O95563 (AlphaFold model) |
| Fab_8D3_2 heavy chain | D | protein | 265 | Mus musculus | |
| Fab_8D3_2 light chain | E | protein | 247 | Mus musculus | |
| Nanobody | C | protein | 152 | synthetic construct | |
| Mbp-pra/g | F | protein | 545 | Escherichia coli | |
Sequence of entity 1 (A), FASTA
>9MNW_1 Mitochondrial pyruvate carrier 1 (chains A)
MAGALVRKAADYVRSKDFRDYLMSTHFWGPVANWGLPIAAINDMKKSPEIISGRMTFALC
CYSLTFMRFAYKVQPRNWLLFACHATNEVAQLIQGGRLIKHEMTKTASALEVLFQ
Sequence of entity 2 (B), FASTA
>9MNW_2 Mitochondrial pyruvate carrier 2 (chains B)
MSAAGARGLRATYHRLLDKVELMLPEKLRPLYNHPAGPRTVFFWAPIMKWGLVCAGLADM
ARPAEKLSTAQSAVLMATGFIWSRYSLVIIPKNWSLFAVNFFVGAAGASQLFRIWRYNQE
LKAKAHK
Sequence of entity 3 (D), FASTA
>9MNW_3 Fab_8D3_2 heavy chain (chains D)
MDWTWRVFCLLAVAPGAHSDVQLVESGGGLVQPGKSLRLSCAASGFTFSNFGMHWVRQAP
EMGLEWVAYISSGSTTKYYGDTVKGRFTISRDNPKNTLYLQMNSLRSEDTAMYYCARRPL
YDGDYGYPMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVT
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV
EPKSCGSLEVLFQGPHHHHHHHHHH
Sequence of entity 4 (E), FASTA
>9MNW_4 Fab_8D3_2 light chain (chains E)
MVLQTQVFISLLLWISGAYGNIMLTQSPSSLAVSAGERVTMSCKSTQSILYNSNQKTYLA
WYQQKPGQSPKLLIYWASTRASGVPDRFTGSGSGTDFTLTINSVQPEDLAVYYCHQYLSA
WTFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ
SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECW
SHPQFEK
Sequence of entity 5 (C), FASTA
>9MNW_5 Nanobody (chains C)
MKYLLPTAAAGLLLLAAQPAMAQVQLQESGGGLVQAGGSLRLSCAASGTIFYYGTMGWYR
QAPGKERELVASINRGGNTNYADSVKGRFTISRDNAKNTVYLQMNSLKPEDTAVYYCAVK
SGLIYAHRYWGQGTQVTVSSLEHHHHHHHHHH
Sequence of entity 6 (F), FASTA
>9MNW_6 MBP-PrA/G (chains F)
MKIEEGKLVIWINGDKGYNGLAEVGKKFEKDTGIKVTVEHPDKLEEKFPQVAATGDGPDI
IFWAHDRFGGYAQSGLLAEITPDKAFQDKLYPFTWDAVRYNGKLIAYPIAVEALSLIYNK
DLLPNPPKTWEEIPALDKELKAKGKSALMFNLQEPYFTWPLIAADGGYAFKYENGKYDIK
DVGVDNAGAKAGLTFLVDLIKNKHMNADTDYSIAEAAFNKGETAMTINGPWAWSNIDTSK
VNYGVTVLPTFKGQPSKPFVGVLSAGINAASPNKELAKEFLENYLLTDEGLEAVNKDKPL
GAVALKSYEEELAKDPRIAATMENAQKGEIMPNIPQMSAFWYAVRTAVINAASGRQTVDQ
ALAFAQILIMPNLTEEQRNGFIQSLKDDPSVSKEILAEAKKLNEHQAPKGGSGGAGSGDQ
QSAFYEILNMPNLNEAQRNGFIQSLKDDPSQSTNVLGEAKKLNESQAGGGSGGGSGGSAV
TTYKLVINGKTLKGETTTKAVDAETAEKAFKQYANDNGVDGVWTYDDATKTFTVTEGSGH
HHHHH
Ligands and cofactors
| ID | Name | Formula | Copies |
|---|
| A1BM8 | (5E)-5-({(5P)-5-[6-(4-acetylpiperazin-1-yl)-3-nitropyridin-2-yl]-2-fluorophenyl… | C21 H18 F N5 O5 S | 1 |
Primary citation
Structure of mitochondrial pyruvate carrier and its inhibition mechanism. He, Z., Zhang, J., Xu, Y. et al. Nature (2025) 641:250-257. DOI 10.1038/s41586-025-08667-y · PubMed
Other PDB entries of the same protein (UniProt Q9Y5U8 (AlphaFold model), which also has an AlphaFold model), best resolution first:
- 9MNZ 2.73 Å, Cryo-EM structure of human MPC in complex with UK5099 in nanodiscs
- 9MNY 2.78 Å, Cryo-EM structure of human MPC with pyruvate
- 9MO0 2.83 Å, Cryo-EM structure of human MPC in complex with AKOS005153046
- 8YW9 3.01 Å, Cryo-EM structure of human mitochondrial pyruvate carrier in the matrix-facing…
- 9MNX 3.11 Å, Cryo-EM structure of human MPC in complex with UK5099 in LMNG
- 8YW8 3.17 Å, Cryo-EM structure of human mitochondrial pyruvate carrier in complex with the inhibitor…
- 8YW6 3.18 Å, Cryo-EM structure of apo human mitochondrial pyruvate carrier in the IMS-open…
- 9O9T 3.31 Å, Structure of human MPC IMS-open
- 9KNY 3.4 Å, Cryo-EM structure of pyruvate-treated human mitochondrial pyruvate carrier in the…
- 9KNW 3.41 Å, Cryo-EM structure of apo human mitochondrial pyruvate carrier in the IMS-open…
- 9O9S 3.57 Å, Structure of human MPC matrix-open
- 9KNX 3.72 Å, Cryo-EM structure of human mitochondrial pyruvate carrier in the occluded conformation…
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