2LE3

N-terminal regulatory segment of carnitine palmitoyltransferase 1A


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 20 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

An Environment-dependent Structural Switch Underlies the Regulation of Carnitine Palmitoyltransferase 1A.

Rao, J.N.Warren, G.Z.Estolt-Povedano, S.Zammit, V.A.Ulmer, T.S.

(2011) J Biol Chem 286: 42545-42554

  • DOI: https://doi.org/10.1074/jbc.M111.306951
  • Primary Citation of Related Structures:  
    2LE3

  • 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.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology and Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, California 90033.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carnitine O-palmitoyltransferase 1, liver isoform42Homo sapiensMutation(s): 0 
Gene Names: CPT1ACPT1
EC: 2.3.1.21
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P50416 (Homo sapiens)
Explore P50416 
Go to UniProtKB:  P50416
PHAROS:  P50416
GTEx:  ENSG00000110090 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP50416
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 20 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-10-19
    Type: Initial release
  • Version 1.1: 2011-12-28
    Changes: Database references
  • Version 1.2: 2023-06-14
    Changes: Data collection, Database references, Other
  • Version 1.3: 2024-05-15
    Changes: Data collection, Database references