The peroxisomal receptor Pex19p forms a helical mPTS recognition domain

Area of Science:

• Cell Biology
• Structural Biology
• Biochemistry

Background:

• Pex19p is a key receptor and chaperone for peroxisomal membrane proteins (PMPs).
• Understanding Pex19p's structure-function relationship is vital for peroxisome biogenesis.

Purpose of the Study:

• To elucidate the structural basis of Pex19p's interaction with PMP-targeting signals (mPTS).
• To investigate the role of specific Pex19p domains in PMP recognition and import.

Main Methods:

• X-ray crystallography to determine the structure of the Pex19p C-terminal domain.
• Functional assays using truncated Pex19p constructs and site-directed mutagenesis.
• Analysis of Pex19p variants' ability to bind mPTS and mediate cargo import.

Main Results:

• The crystal structure revealed a globular domain with a three-helix bundle in the Pex19p C-terminus.
• The structured alpha-helical domain binds mPTS sequences with a dissociation constant (Kd) of approximately 10 muM.
• A conserved N-terminal helical segment within this domain is essential for mPTS binding and proper PMP import.
• Mutations in this segment abolish Pex19p's function in cargo import.

Conclusions:

• Pex19p possesses a distinct mPTS recognition domain within its C-terminal structure.
• This domain, including a conserved N-terminal helical segment, is critical for mediating PMP import.
• Pex19p exhibits a modular N-terminal and C-terminal organization, facilitating separate functions like signal recognition and potentially others, similar to the Pex5p receptor.