Complete three-dimensional structures of the Lon protease translocating a protein substrate

Area of Science:

• Molecular Biology
• Structural Biology
• Biochemistry

Background:

• The Lon protease is a conserved cellular machine responsible for degrading misfolded and damaged proteins, as well as specific substrates.
• It features a hexameric core composed of ATPase and protease domains, with a large N-terminal domain.

Purpose of the Study:

• To elucidate the complete structural mechanisms of the Lon protease when engaging with a substrate.
• To provide a detailed framework for understanding Lon's function in protein degradation and quality control.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was utilized to determine the structures.
• High-resolution structures (2.4-angstrom) of Lon bound to a substrate were obtained.

Main Results:

• Two complete structures of Lon engaging a substrate were resolved.
• A multilayered architecture was revealed, including a unique tensegrity triangle complex formed by N-terminal helices.
• This complex acts as a platform controlling substrate access, selection, and unfolding.

Conclusions:

• The study provides a comprehensive structural framework for understanding the Lon protease.
• The unique architecture facilitates substrate processing through controlled access, selection, and unfolding mechanisms.
• This work deepens insights into the molecular mechanisms underlying protein homeostasis and degradation.