Abstract

PTS1, peroxisomal targeting signal 1, is one of two peroxisomal import
signals which direct proteins into the lumen (matrix) of the peroxisome.
(The other being PTS2.) A third signal is used to target peroxisomal
membrane proteins.
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PTS1 was first clearly defined by Gould et al. (1989) following earlier
work from the same group. Reviews of peroxisome biogenesis and import
include Kunau (2001), Purdue and Lazarow (2001), Terlecky and Franzen
(2000), Holroyd and Erdmann (2001), Subramani et al. (2000) and Fujiki
(2000).
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The functions of peroxisomes vary in different cell types or organisms
and some specialised peroxisomes have other names. A generic term for
all these organelles is microbody. Glyoxysomes provide the glycolytic
cycle in germinating plant seeds. Glycosomes perform glycolysis in
trypanosomatids. Cholesterol synthesis occurs in animal peroxisomes. Two
widely conserved functions are H2O2-based respiration and beta-oxidation
of fatty acids.
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Pex5p (Peroxin 5) protein is the receptor for PTS1 (P50542).
It imports folded proteins (and probably even imports pre-assembled
complexes since some peroxisomal proteins lack obvious PTS signals). The
import machinery is clearly complex and Pex5p interacts with several
other proteins involved in peroxisome import, including Pex8p, 10p, 12p,
13p, 14p. During import, Pex5p is thought to shuttle between the cytosol
and the peroxisomal matrix. Earlier names for Pex5p are Pas8 and Pxr1.
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A structure of the Pex5p-PTS1 complex (1FCH) has been solved (Gatto et
al., 2000). Pex5p has 6 rod-forming TPR (tetratricopeptide) repeats,
split 3-3, which fold at a hinge region to sandwich PTS1 in a cleft. The
structure shows many details of the molecular recognition of PTS1 by
Pex5p, including tight interaction with the C-terminal carboxyl group.
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The presence of PTS1 on a protein does not exclude alternative cellular
locations, particularly in the cytoplasm or mitochondrion. For
example mitochondria and peroxisomes have partially duplicated lipid
biochemistry. Several proteins are targeted to both mitochondria and
peroxisomes, either because of alternatively-spliced gene products or
because both targeting signals are present on the same protein.
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Mutations in Pex5p define complementation group 2 of the peroxisome
biogenesis disorders (PBDs), such as Zellweger syndrome (see
OMIM:214100, OMIM:600414, OMIM:202370). These disorders are
characterised by an absence of peroxisomes, multiple enzymatic
deficiencies and physical malformation.
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See also PROSITE entry for PTS1: PS00342.
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The classical PTS1 motif is SKL$, with similar residues tolerated at
each position. It has also been noted that PTS1s lacking the positively
charged residue are then preceded by a K or R, presumably in binding
affinity compensation, e.g. KANL$ is the PTS1 in human catalase. The
current pattern will detect most examples in any eukaryote. There is no
strong taxonomic divergence (as of 2002) although there may be scope for
some future revision of the pattern. For example, Ala in the third (Leu)
position has been seen in one or two yeast candidate PTS1s.