Acyl modification and binding of mitochondrial ACP to multiprotein complexes
Heike Angerer1, Stefan Schönborn2, Jan Gorka2
1Goethe University Frankfurt, Medical School, Institute of Biochemistry II, Structural Bioenergetics Group, Max-von-Laue Str. 9, 60438 Frankfurt, Germany.
Abstract:
The mitochondrial acyl carrier protein (ACPM/NDUFAB1) is a central element of the mitochondrial fatty acid synthesis type II machinery. Originally ACPM was detected as a subunit of respiratory complex I but the reason for the association with the large enzyme complex remained elusive. Complex I from the aerobic yeast Yarrowia lipolytica comprises two different ACPMs, ACPM1 and ACPM2. They are anchored to the protein complex by LYR (leucine-tyrosine-arginine) motif containing protein (LYRM) subunits LYRM3 (NDUFB9) and LYRM6 (NDUFA6). The ACPM1-LYRM6 and ACPM2-LYRM3 modules are essential for complex I activity and assembly/stability, respectively. We show that in addition to the complex I bound fraction, ACPM1 is present as a free matrix protein and in complex with the soluble LYRM4(ISD11)/NFS1 complex implicated in Fe-S cluster biogenesis. We show that the presence of a long acyl chain bound to the phosphopantetheine cofactor is important for docking ACPMs to protein complexes and we propose that association of ACPMs and LYRMs is universally based on a new protein-protein interaction motif.
Insights
Mitochondrial acyl carrier proteins (ACPMs) are crucial for fatty acid synthesis and complex I function. Their interaction with LYR motif proteins is vital for complex assembly and stability.
Area of Science:
- Mitochondrial biology
- Protein biochemistry
- Enzyme complex assembly
Background:
- Mitochondrial acyl carrier protein (ACPM/NDUFAB1) is key to fatty acid synthesis type II.
- ACPM's role as a respiratory complex I subunit was previously unclear.
- Yarrowia lipolytica's Complex I has two ACPMs (ACPM1, ACPM2) linked by LYRM subunits.
Purpose of the Study:
- Investigate the function and interactions of ACPMs in yeast Complex I.
- Elucidate the role of ACPM-LYRM interactions in complex assembly and activity.
- Determine the structural basis for ACPM-LYRM association.
Main Methods:
- Protein complex isolation and characterization.
- Yeast genetics and molecular biology techniques.
- Biochemical assays for complex I activity and assembly.
Main Results:
- ACPM1 exists both bound to Complex I and as a free protein.
- ACPM1 also forms complexes with LYRM4(ISD11)/NFS1 involved in Fe-S cluster biogenesis.
- A long acyl chain on the phosphopantetheine cofactor is essential for ACPM docking to protein complexes.
- A novel protein-protein interaction motif mediating ACPM-LYRM association is proposed.
Conclusions:
- ACPMs have multifaceted roles beyond fatty acid synthesis, including Complex I assembly and Fe-S cluster biogenesis.
- Specific ACPM-LYRM interactions are critical for Complex I function and stability.
- A conserved interaction motif likely governs ACPM-LYRM binding across different protein complexes.
More Related Videos
05:45Author Spotlight: Unveiling Oxidative Phosphorylation System Dynamics and Mitochondrial Roles in Health and Disease
Published on: May 3, 2024
08:37Analyzing Supercomplexes of the Mitochondrial Electron Transport Chain with Native Electrophoresis, In-gel Assays, and Electroelution
Published on: June 1, 2017
Related Concept Videos
The ADP/ATP Carrier Protein
Mitochondrial Protein Sorting
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Translocation of Proteins into the Mitochondria
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Covalently Linked Protein Regulators
These groups modify specific amino acids in a protein....
The Supercomplexes in the Crista Membrane
Mitochondrial Precursor Proteins
Most of the mitochondrial...
