2LE3

N-terminal regulatory segment of carnitine palmitoyltransferase 1A

2LE3 の概要

• エントリーDOI: 10.2210/pdb2le3/pdb
• NMR情報: BMRB: 17690
• 分子名称: Carnitine O-palmitoyltransferase 1, liver isoform (1 entity in total)
• 機能のキーワード: membrane protein, amphiphilic structure, membrane-protein interaction, structural switch, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion outer membrane; Multi-pass membrane protein: P50416
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4802.51

構造登録者

Ulmer, T.S.,Rao, J.N. (登録日: 2011-06-06, 公開日: 2011-10-19, 最終更新日: 2024-05-15)

主引用文献

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

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: 21990363
DOI: 10.1074/jbc.M111.306951

実験手法

SOLUTION NMR