InterPro domain: IPR004815

Lon protease belongs to the S16 peptidase family and is an ATP-dependent serine protease that mediates the selective degradation of mutant and abnormal proteins, as well as certain short-lived regulatory proteins. It is required for cellular homeostasis and for survival from DNA damage and developmental changes induced by stress [ 1 ]. In pathogenic bacteria, it is required for the expression of virulence genes that promote cell infection [ 2 ].

Lon (La) protease was the first ATP-dependent protease to be purified fromE. coli [ 3 , 4 , 5 , 6 ]. The enzyme is a homotetramer of 87kDa subunits, with one proteolytic and one ATP-binding site per monomer, making it structurally less complex than other known ATP-dependent proteases [ 7 ]. Despite this relative structural simplicity, Lon recognises its substrates directly, without delegating the task of substrate recognition to other enzymes [ 7 ].

This signature defines the bacterial and eukaryotic lon proteases. This family of sequences does not include the archaeal lon homologues, IPR004663 . In the eukaryotes the majority of the proteins are located in the mitochondrial matrix [ 7 , 8 ]. The yeast homologue, Pim1, is required for mitochondrial function and is constitutively expressed, but is increased after thermal stress, suggesting that Pim1 may play a role in the heat shock response [ 9 ].

1. Recent developments in the mechanistic enzymology of the ATP-dependent Lon protease from Escherichia coli: highlights from kinetic studies. Mol Biosyst 2, 477-83
2. The Brucella abortus Lon functions as a generalized stress response protease and is required for wild-type virulence in BALB/c mice. Mol. Microbiol. 35, 577-88
3. The lon protease from Mycobacterium smegmatis: molecular cloning, sequence analysis, functional expression, and enzymatic characterization. Biochemistry 37, 377-86
4. Sequence of the lon gene in Escherichia coli. A heat-shock gene which encodes the ATP-dependent protease La. J. Biol. Chem. 263, 11718-28
5. Controlled high-level expression of the lon gene of Escherichia coli allows overproduction of Lon protease. Gene 136, 237-42
6. ATP hydrolysis is not stoichiometrically linked with proteolysis in the ATP-dependent protease La from Escherichia coli. J. Biol. Chem. 268, 22502-7
7. A human mitochondrial ATP-dependent protease that is highly homologous to bacterial Lon protease. Proc. Natl. Acad. Sci. U.S.A. 90, 11247-51
8. Maize contains a Lon protease gene that can partially complement a yeast pim1-deletion mutant. Plant Mol. Biol. 37, 141-54
9. PIM1 encodes a mitochondrial ATP-dependent protease that is required for mitochondrial function in the yeast Saccharomyces cerevisiae. J. Biol. Chem. 269, 238-42