Are proteins translocated through pores? An historical overview

Area of Science:

• Cell Biology
• Biophysics
• Molecular Biology

Background:

• Traditionally, proteinaceous pores were identified as ionic channels.
• Emerging evidence highlights their role in protein translocation across phospholipidic membranes.
• This evolving concept necessitated advancements in electrical and biochemical methodologies.

Purpose of the Study:

• To explore the distinct nature of protein-conducting pores compared to ionic channels.
• To elucidate the mechanisms and biological significance of protein translocation through these pores.
• To detail the involvement of these pores in various cellular processes and membrane protein insertion.

Main Methods:

• Development and application of adapted electrical and biochemical methods.
• Single-molecule level electrical analysis of pore activity.
• Molecular and atomic level investigations of pore structure and function.

Main Results:

• Protein-conducting pores are integral to mitochondrial biogenesis, endoplasmic reticulum secretion, and bacterial toxin internalization.
• These pores exhibit large conductance, requiring tight regulation to prevent ion leakage.
• They are involved in both protein translocation and the insertion of membrane proteins (alpha-helix and beta-barrel).

Conclusions:

• Protein-conducting pores represent a distinct paradigm from neurobiological ionic channels.
• These pores are often components of large molecular complexes and provide real-time, single-molecule insights via electrical analysis.
• Their established role extends to protein translocation and diverse membrane protein insertion mechanisms.