Crystal structure of peroxisomal targeting signal-2 bound to its receptor complex Pex7p-Pex21p.
D.Pan,
T.Nakatsu,
H.Kato.
ABSTRACT
Appropriate targeting of matrix proteins to peroxisomes is mainly directed by
two types of peroxisomal targeting signals, PTS1 and PTS2. Although the basis of
PTS1 recognition has been revealed by structural studies, that of PTS2
recognition remains elusive. Here we present the crystal structure of a
heterotrimeric PTS2-recognition complex from Saccharomyces cerevisiae,
containing Pex7p, the C-terminal region of Pex21p and the PTS2 of the
peroxisomal 3-ketoacyl-CoA thiolase. Pex7p forms a β-propeller structure and
provides a platform for cooperative interactions with both the amphipathic PTS2
helix and Pex21p. The C-terminal region of Pex21p directly covers the
hydrophobic surfaces of both Pex7p and PTS2, and the resulting hydrophobic core
is the primary determinant of stable complex formation. Together with in vivo
and in vitro functional assays of Pex7p and Pex21p variants, our findings reveal
the molecular mechanism of PTS2 recognition.