Crystal structure of Lon protease: molecular architecture of gated entry to a sequestered degradation chamber

EMBO J. 2010 Oct 20;29(20):3520-30. doi: 10.1038/emboj.2010.226. Epub 2010 Sep 10.


Lon proteases are distributed in all kingdoms of life and are required for survival of cells under stress. Lon is a tandem fusion of an AAA+ molecular chaperone and a protease with a serine-lysine catalytic dyad. We report the 2.0-Å resolution crystal structure of Thermococcus onnurineus NA1 Lon (TonLon). The structure is a three-tiered hexagonal cylinder with a large sequestered chamber accessible through an axial channel. Conserved loops extending from the AAA+ domain combine with an insertion domain containing the membrane anchor to form an apical domain that serves as a gate governing substrate access to an internal unfolding and degradation chamber. Alternating AAA+ domains are in tight- and weak-binding nucleotide states with different domain orientations and intersubunit contacts, reflecting intramolecular dynamics during ATP-driven protein unfolding and translocation. The bowl-shaped proteolytic chamber is contiguous with the chaperone chamber allowing internalized proteins direct access to the proteolytic sites without further gating restrictions.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Sequence Data
  • Protease La / chemistry*
  • Protease La / genetics
  • Protease La / metabolism*
  • Protein Multimerization
  • Protein Structure, Quaternary*
  • Protein Structure, Tertiary*
  • Sequence Alignment
  • Thermococcus / enzymology


  • Bacterial Proteins
  • Protease La

Associated data

  • PDB/3K1J