The peroxisomal importomer constitutes a large and highly dynamic pore

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Peroxisomal protein import differs from other cellular translocons, allowing passage of folded proteins.
• The precise mechanism of protein translocation across the peroxisomal membrane is not fully understood.
• Existing models include membrane invagination, vesicle fusion, or large import pores.

Purpose of the Study:

• To elucidate the mechanistic principles of protein translocation across the peroxisomal membrane.
• To investigate the role of the import receptor Pex5p in forming an import pore.
• To characterize the structure and dynamics of the peroxisomal import machinery.

Main Methods:

• Demonstration of a gated ion-conducting channel formed by Pex5p and Pex14p.
• Characterization of channel opening by cytosolic receptor-cargo complexes.
• Analysis of channel dynamics during protein translocation.

Main Results:

• The membrane-associated import receptor Pex5p and its partner Pex14p form a gated ion-conducting channel.
• This channel can open to a diameter of approximately 9 nm when bound to cytosolic receptor-cargo complexes.
• The identified pore exhibits dynamic behavior consistent with the translocation of variable-sized proteins.

Conclusions:

• The Pex5p-Pex14p complex forms a functional import pore for peroxisomal proteins.
• This pore is gated and dynamically regulated by cargo binding.
• The findings support the transient pore hypothesis for peroxisomal protein import.