Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structures and mechanism of the human mitochondrial pyruvate carrier.
Journal, issue, pages	Nature, Vol. 641, Issue 8061, Page 258-265, Year 2025
Publish date	Mar 18, 2025
Authors	Jiaming Liang / Junhui Shi / Ailong Song / Meihua Lu / Kairan Zhang / Meng Xu / Gaoxingyu Huang / Peilong Lu / Xudong Wu / Dan Ma /
PubMed Abstract	The mitochondrial pyruvate carrier (MPC) is a mitochondrial inner membrane protein complex that is essential for the uptake of pyruvate into the mitochondrial matrix as the primary carbon source for ...The mitochondrial pyruvate carrier (MPC) is a mitochondrial inner membrane protein complex that is essential for the uptake of pyruvate into the mitochondrial matrix as the primary carbon source for the tricarboxylic acid cycle. Here we present six cryo-electron microscopy structures of human MPC in three states: three structures in the intermembrane space (IMS)-open state, obtained in different conditions; a structure of pyruvate-treated MPC in the occluded state; and two structures in the matrix-facing state, bound with the inhibitor UK5099 or with an inhibitory nanobody on the matrix side. MPC is a heterodimer consisting of MPC1 and MPC2, with the transmembrane domain adopting pseudo-C2 symmetry. Approximate rigid-body movements occur between the IMS-open state and the occluded state, whereas structural changes, mainly on the matrix side, facilitate the transition between the occluded state and the matrix-facing state, revealing an alternating access mechanism during pyruvate transport. In the UK5099-bound structure, the inhibitor fits well and interacts extensively with a pocket that opens to the matrix side. Our findings provide key insights into the mechanisms that underlie MPC-mediated substrate transport, and shed light on the recognition and inhibition of MPC by UK5099, which will facilitate the future development of drugs that target MPC.
External links	Nature / PubMed:40101766
Methods	EM (single particle)
Resolution	3.01 - 3.72 Å
Structure data	39624 8yw6 EMDB-39624, PDB-8yw6: Cryo-EM structure of apo human mitochondrial pyruvate carrier in the IMS-open conformation at pH 8.0 Method: EM (single particle) / Resolution: 3.18 Å 39625 8yw8 EMDB-39625, PDB-8yw8: Cryo-EM structure of human mitochondrial pyruvate carrier in complex with the inhibitor UK5099 Method: EM (single particle) / Resolution: 3.17 Å 39626 8yw9 EMDB-39626, PDB-8yw9: Cryo-EM structure of human mitochondrial pyruvate carrier in the matrix-facing conformation at pH 6.8 Method: EM (single particle) / Resolution: 3.01 Å 62464 9knw EMDB-62464, PDB-9knw: Cryo-EM structure of apo human mitochondrial pyruvate carrier in the IMS-open conformation at pH 6.8 Method: EM (single particle) / Resolution: 3.41 Å 62465 9knx EMDB-62465, PDB-9knx: Cryo-EM structure of human mitochondrial pyruvate carrier in the occluded conformation at pH 6.8 Method: EM (single particle) / Resolution: 3.72 Å 62466 9kny EMDB-62466, PDB-9kny: Cryo-EM structure of pyruvate-treated human mitochondrial pyruvate carrier in the IMS-open conformation at pH 8.0 Method: EM (single particle) / Resolution: 3.4 Å
Chemicals	ChemComp-PC8: 1,2-DIOCTANOYL-SN-GLYCERO-3-PHOSPHOCHOLINE ChemComp-CDL: CARDIOLIPIN / phospholipidYM ChemComp-I2R: (E)-2-cyano-3-(1-phenylindol-3-yl)prop-2-enoic acid / inhibitorYM
Source	homo sapiens (human) synthetic construct (others) escherichia coli bl21(de3) (bacteria)
Keywords	PROTEIN TRANSPORT / mitochondrial pyruvate carrier / MPC / pyruvate transport / A membrane transporter complex with substrate