Disordered-to-ordered transitions in assembly factors allow the complex II catalytic subunit to switch binding...

Area of Science:

• Biochemistry
• Molecular Biology
• Cellular Metabolism

Background:

• Complex II (CII) activity is crucial for cellular metabolism and signaling pathways.
• CII function is implicated in various diseases, including neurodegeneration and cancer.
• Regulation of CII assembly via metastable intermediates is poorly understood.

Purpose of the Study:

• To identify and characterize metastable assembly intermediates of Complex II.
• To elucidate the temporal sequence and structural dynamics of CII subunit assembly.
• To understand the role of intrinsically disordered regions in Complex II assembly regulation.

Main Methods:

• Cryo-electron microscopy (Cryo-EM) to determine structures of assembly intermediates.
• Biochemical assays to analyze subunit interactions and assembly dynamics.
• Bioinformatics analysis of intrinsically disordered regions in CII subunits.

Main Results:

• Identified metastable species containing the SDHA subunit and assembly factors.
• Established a preferred temporal sequence for the appearance of these species during CII assembly.
• Structural analysis revealed disordered-to-ordered transitions in assembly factors without significant secondary structure formation.

Conclusions:

• Intrinsically disordered regions are critical regulators of Complex II assembly.
• The findings provide insights into the dynamic process of mitochondrial complex assembly.
• Understanding CII assembly mechanisms has implications for therapeutic strategies targeting metabolic disorders.