A multipoint guidance mechanism for β-barrel folding on the SAM complex

Area of Science:

• Biochemistry
• Cell Biology
• Structural Biology

Background:

• Mitochondrial beta-barrel proteins are crucial for cellular functions, including transport.
• The sorting and assembly machinery (SAM) complex is essential for their correct folding and membrane insertion.
• Understanding the SAM complex mechanism is key to comprehending mitochondrial protein biogenesis.

Purpose of the Study:

• To elucidate the structural mechanism of mitochondrial beta-barrel protein folding by the SAM complex.
• To visualize the interaction between the SAM complex and a folding intermediate of a beta-barrel protein.
• To reveal the step-by-step guidance provided by the SAM complex during protein assembly.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was used to determine the structure of the yeast SAM complex.
• The structure captured an early eukaryotic beta-barrel folding intermediate.
• High-resolution imaging allowed visualization of protein-protein interactions during folding.

Main Results:

• The cryo-EM structure revealed the Sam50 component of the SAM complex with an open lateral gate.
• This gate interacts with the final beta-strand of the Tom40 precursor, forming a hybrid barrel structure.
• The study identified a multipoint guidance mechanism involving Sam50, Sam37, and the substrate, Tom40, during barrel formation.

Conclusions:

• The SAM complex employs a sophisticated multipoint guidance mechanism to ensure accurate mitochondrial beta-barrel protein folding.
• This mechanism involves dynamic interactions between SAM components and the substrate, guiding its assembly step-by-step.
• The findings provide critical insights into the biogenesis of essential mitochondrial proteins.