Presequence protease

Presequence protease
	Crystal structure of A. thaliana PreP PDP 2fge
	Existing structural data : 2fge
Properties of human protein
Secondary to quaternary structure	Homodimer
Cofactor	Zn 2+
Identifier
Gene name	PITRM1
External IDs	UniProt : Q5JRX3 ; MGI : 1916867 ;
Enzyme classification
EC, category	3.4.24. , Metalloprotease
MEROPS	M16.009
Occurrence
Homology family	Presence protease
Parent taxon	Euteleostomi
	Orthologue

The presequence protease ( PreP ) is an enzyme that occurs in the mitochondria and, in plants, also in the chloroplasts .

function

PreP is a metalloprotease with a zinc finger motif in the catalytic center. It is found in most eukaryotic organisms and is responsible for the breakdown of unstructured peptides that are between 10 and 60 amino acids long. PreP breaks down the pre-sequence, which serves as an address for the transport of pre-proteins into the corresponding organelle . The breakdown of short peptides in mitochondria and chloroplasts is necessary because these pass through the membranes and in this way decouple the electron transport chain and disrupt the membrane potential .

Most of the mitochondrial and chloroplastic proteins encoded in the cell nucleus are synthesized in the cytosol as precursor proteins with a pre-sequence. This pre-sequence is an N-terminal extension, a so-called signal peptide or “targeting signal”. In plants this signal is 30-50 amino acids long, contains many hydroxylated, hydrophobic and basic amino acids and interacts with the membrane. After being transported through the mitochondrial membranes, this signal is cut off by a mitochondrial processing peptidase (MPP) and recognized and broken down by PreP, which has a preference for basic and small amino acids or serines at the cutting site.

Isoforms

In Arabidopsis thaliana there are two isoforms , At PreP1 and At PreP2, and they weigh about 100 kDa . They are soluble enzymes and occur only in the mitochondrial matrix and in the stroma of the chloroplasts. Since the import into mitochondria and chloroplasts is usually very specific, this is a case of "dual targeting" - the same sequence leads to import into two different organelles.

Breakdown of amyloid-β

Human PreP breaks down amyloid-β peptides and thus could play a role in the treatment of Alzheimer's disease .

literature

E. Glaser, S. Nilsson, S. Bhushan: Two novel mitochondrial and chloroplastic targeting-peptide-degrading peptidasomes in A. thaliana , At PreP1 and At PreP2 . (2006) Biol. Chem., Vol. 387. PMID 17081117 .