2LE3
N-terminal regulatory segment of carnitine palmitoyltransferase 1A
Summary for 2LE3
| Entry DOI | 10.2210/pdb2le3/pdb |
| NMR Information | BMRB: 17690 |
| Descriptor | Carnitine O-palmitoyltransferase 1, liver isoform (1 entity in total) |
| Functional Keywords | membrane protein, amphiphilic structure, membrane-protein interaction, structural switch, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Mitochondrion outer membrane; Multi-pass membrane protein: P50416 |
| Total number of polymer chains | 1 |
| Total formula weight | 4802.51 |
| Authors | Ulmer, T.S.,Rao, J.N. (deposition date: 2011-06-06, release date: 2011-10-19, Last modification date: 2024-05-15) |
| Primary citation | Rao, J.N.,Warren, G.Z.,Estolt-Povedano, S.,Zammit, V.A.,Ulmer, T.S. An Environment-dependent Structural Switch Underlies the Regulation of Carnitine Palmitoyltransferase 1A. J.Biol.Chem., 286:42545-42554, 2011 Cited by PubMed Abstract: The enzyme carnitine palmitoyltransferase 1 (CPT1), which is anchored in the outer mitochondrial membrane (OMM), controls the rate-limiting step in fatty acid β-oxidation in mammalian tissues. It is inhibited by malonyl-CoA, the first intermediate of fatty acid synthesis, and it responds to OMM curvature and lipid characteristics, which reflect long term nutrient/hormone availability. Here, we show that the N-terminal regulatory domain (N) of CPT1A can adopt two complex amphiphilic structural states, termed Nα and Nβ, that interchange in a switch-like manner in response to offered binding surface curvature. Structure-based site-directed mutageneses of native CPT1A suggest Nα to be inhibitory and Nβ to be noninhibitory, with the relative Nα/Nβ ratio setting the prevalent malonyl-CoA sensitivity of the enzyme. Based on the amphiphilic nature of N and molecular modeling, we propose malonyl-CoA sensitivity to be coupled to the properties of the OMM by Nα-OMM associations that alter the Nα/Nβ ratio. For enzymes residing at the membrane-water interface, this constitutes an integrative regulatory mechanism of exceptional sophistication. PubMed: 21990363DOI: 10.1074/jbc.M111.306951 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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