Structural insight into the SAM-mediated assembly of the mitochondrial TOM core complex

Area of Science:

• Biochemistry
• Structural Biology
• Cell Biology

Background:

• Beta barrel outer membrane proteins (β-OMPs) are crucial for cellular functions in mitochondria, chloroplasts, and bacteria.
• The mitochondrial sorting and assembly machinery (SAM) complex is essential for the biogenesis of β-OMPs.
• Understanding the assembly mechanism of β-OMP complexes is vital for comprehending cellular organization and function.

Purpose of the Study:

• To investigate the role of the SAM complex in the assembly of the translocase of the outer membrane (TOM) core complex.
• To elucidate the structural basis of SAM-mediated β-OMP assembly.
• To provide insights into the molecular interactions governing the release of β-barrel complexes.

Main Methods:

• Cryo-electron microscopy (Cryo-EM) was employed to determine high-resolution structures.
• Structures of the SAM complex with the Tom40 protein, both alone and in complex with Tom5 and Tom6, were obtained.
• Analysis of electrostatic interactions between Sam37 and Tom40 was performed.

Main Results:

• High-resolution Cryo-EM structures (~3 angstroms) of SAM-Tom40 and SAM-Tom40/Tom5/Tom6 complexes were determined.
• Sam37 was found to stabilize the mature Tom40 protein primarily through electrostatic interactions.
• These interactions are crucial for facilitating the subsequent assembly steps of the TOM complex.

Conclusions:

• The findings support the beta barrel switching model for protein assembly.
• Structural insights reveal the mechanism by which Sam37 facilitates Tom40 maturation and release.
• This study enhances our understanding of the intricate process of β-OMP assembly in cellular compartments.