Protein transport via amino-terminal targeting sequences: common themes in diverse systems (Review)

Abstract

Many proteins that are synthesized in the cytoplasm of cells are ultimately found in non-cytoplasmic locations. The correct targeting and transport of proteins must occur across bacterial cell membranes, the endoplasmic reticulum membrane, and those of mitochondria and chloroplasts. One unifying feature among transported proteins in these systems is the requirement for an amino-terminal targeting signal. Although the primary sequence of targeting signals varies substantially, many patterns involving overall properties are shared. A recent surge in the identification of components of the transport apparatus from many different systems has revealed that these are also closely related. In this review we describe some of the key components of different transport systems and highlight these common features.

Roles of N-Terminal Fatty Acid Acylations in Membrane Compartment Partitioning:Arabidopsis h-Type Thioredoxins as a Case Study

“…The N terminus is frequently modified and is known to regulate a number of crucial cellular processes (reviewed in Rusch and Kendall, 1995;Schatz and Dobberstein, 1996;Varshavsky, 2003;Meinnel and Giglione, 2008b;Arnesen, 2011). Several main functions are attributed to N-terminal protein modifications, such as regulation of protein activity, recognition by other molecules or degradation machinery, anchoring to membranes, integration into a specific signal transduction pathway, assistance in protein folding, or translocation to a specific cellular compartment.…”

Mimicking Cellular Sorting Improves Prediction of Subcellular Localization

“…Most proteins destined for the secretory pathway, the mitochondria and the chloroplast contain N-terminal peptides that are recognized by the translocation machinery. 30,31 The term "signal peptide" is used to describe the peptides in secreted proteins that are cleaved in the endoplasmic reticulum (ER) by signal peptidases; the peptides responsible for targeting proteins to the mitochondria and chloroplast are referred to as "transit peptides". Signal and transit peptides can be recognized by generic prediction methods, that by the detection of these peptides also predict subcellular localization.…”

“…By this criterion, proteins from the secretory pathway are more similar to each other than they are to other intra-cellular proteins. 30 Hence, in our classification scheme these compartments are grouped together and are designated as belonging to the secretory pathway. Technically, we incorporated the ontology through a decision tree with SVMs as the nodes ( Figure 1).…”

Are there dominant membrane protein families with a given number of helices?

“…We used an automated hydrophobicity analysis and the GES scale, 6 taking into account signal sequences. 7 This analysis resulted in the distributions shown in Figure 1. Each protein family, defined as a group of proteins sharing a given number of putative transmembrane helices, is found in a roughly continuous descending incidence from single helix proteins to highly polytopic proteins.…”

“…6 Signal sequences, defined as a hydrophobic stretch of 7 or more amino acids within the 25 amino-terminal residues of the protein that is preceded by a net positive charge, were omitted from the analysis. 7 PROTEINS: Structure, Function, and Genetics 28: 465-466 (1997) r 1997 WILEY-LISS, INC.…”