MRPS36 provides a structural link in the eukaryotic 2-oxoglutarate dehydrogenase complex

Area of Science:

• Biochemistry
• Molecular Biology
• Cellular Respiration

Background:

• The tricarboxylic acid cycle is central to eukaryotic energy production.
• 2-oxoglutarate dehydrogenase complex (OGDHC) is a key enzyme in this cycle, generating NADH.
• OGDHC was traditionally considered a three-subunit complex (E1o, E2o, E3).

Purpose of the Study:

• To investigate the role of MRPS36 in the eukaryotic OGDHC.
• To elucidate the structural and functional differences between eukaryotic and prokaryotic OGDHC.
• To provide a refined structural model and mechanistic insights into eukaryotic OGDHC.

Main Methods:

• Cross-linking mass spectrometry
• Phylogenetic analyses
• Comparative sequence analysis
• Computational structure prediction

Main Results:

• MRPS36 is identified as a crucial component of the eukaryotic OGDHC, absent in prokaryotes.
• Eukaryotic E2o lacks the peripheral subunit-binding domain (PSBD) found in bacteria and archaea.
• MRPS36 functions as an E3 adaptor protein, functionally substituting for the PSBD.

Conclusions:

• MRPS36 is an integral part of the eukaryotic OGDHC, essential for its function.
• The eukaryotic OGDHC structure differs significantly from its prokaryotic counterparts.
• A refined structural model of the ~3.45 MDa eukaryotic OGDHC offers new mechanistic insights.