Protein Synthesis and Transport

Protein Synthesis and Targeting

• Proteins are initially synthesized on cytosolic ribosomes and may be dispatched to different destinations based on address labels within their primary sequence.
• Proteins without address labels remain in the cytosol by default.

Nuclear Localization

• Nuclear localization signals (NLS) enable fully folded proteins to move reversibly to the nucleoplasm via nuclear pores.
• NLS is a stretch of 6-8 positive residues anywhere in the primary sequence, recognized by the protein importin.
• Nuclear translocation is regulated by unmasking a NLS for many proteins.

Mitochondrial Targeting

• Proteins destined for mitochondria are fully translated and later modified.
• There are four destinations for proteins in the mitochondria: inner membrane, outer membrane, inter-membrane space, and matrix.
• For matrix proteins, an N-terminal amphipathic helix is recognized by a chaperone protein.

Peroxisomal Targeting

• Proteins destined for peroxisomes have a C-terminal SKL-e sequence, recognized by a PTS1 receptor.
• This targeting mechanism is non-functional in Zellweger syndrome.

General Targeting Principles

• All proteins must cross a membrane, requiring partial unfolding to be threaded through a protein pore within the target membrane.
• Targeting to peroxisomes and mitochondria is irreversible, whereas nuclear translocation is reversible.