Targeting signals required for protein sorting to sub-chloroplast compartments

Chloroplasts, distinctive subcellular organelles found exclusively in plant species, contain three membranes: the outer, inner, and thylakoid membranes. They also have three soluble compartments: the intermembrane space, stroma, and thylakoid lumen. Accordingly, delicate sorting mechanisms are required to ensure proper protein targeting to these sub-chloroplast compartments. Except for most outer membrane proteins, chloroplast interior proteins possess N-terminal cleavable transit peptides as primary import signals. After the cleavage of transit peptides, which occurs during or after import into chloroplasts, the inner and thylakoid membrane proteins, as well as stromal and thylakoid luminal proteins, are further sorted based on additional targeting signals. In this review, we aim to recapitulate the mechanisms by which proteins are targeted to chloroplasts and subsequently sorted into sub-chloroplast compartments, with a focus on the design principles of sorting signals present in chloroplast proteins.