Bacterial Signal Peptides- Navigating the Journey of Proteins

Abstract

In 1971, Blobel proposed the first statement of the Signal Hypothesis which suggested that proteins have amino-terminal sequences that dictate their export and localization in the cell. A cytosolic binding factor was predicted, and later the protein conducting channel was discovered that was proposed in 1975 to align with the large ribosomal tunnel. The 1975 Signal Hypothesis also predicted that proteins targeted to different intracellular membranes would possess distinct signals and integral membrane proteins contained uncleaved signal sequences which initiate translocation of the polypeptide chain. This review summarizes the central role that the signal peptides play as address codes for proteins, their decisive role as targeting factors for delivery to the membrane and their function to activate the translocation machinery for export and membrane protein insertion. After shedding light on the navigation of proteins, the importance of removal of signal peptide and their degradation are addressed. Furthermore, the emerging work on signal peptidases as novel targets for antibiotic development is described.

Signal Peptide Efficiency: From High-Throughput Data to Prediction and Explanation

“…N-terminal signal peptides (SPs) are responsible for guiding secretory proteins into the Sec pathway by interactions with chaperones, the membrane, and the membrane-embedded protein-conducting SecYEG channel and by maintaining an unfolded translocation-competent state of the translocated protein . These ubiquitous targeting signals have been investigated for many years and, consequently, their structural features are well known.…”

“…N-terminal signal peptides (SPs) are responsible for guiding secretory proteins into the Sec pathway by interactions with chaperones, the membrane, and the membrane-embedded protein-conducting SecYEG channel and by maintaining an unfolded translocation-competent state of the translocated protein. 11 These ubiquitous targeting signals have been investigated for many years and, consequently, their structural features are well known. Essentially, SPs are composed of a positively charged N-region, a hydrophobic α-helical H-region, and a more polar C-region that frequently starts with a helix-breaking residue and that comprises the so-called signal peptidase (SPase) recognition site.…”

Phosphatidylglycerol Acts as a Switch for Cholesterol-Dependent Membrane Binding of ApoE Signal Peptide

“…A newly synthesized secretory protein is known to contain a stretch of amino acid residues at the N-terminus, known as the signal peptide (SP), which gets detached from the protein after it has been trafficked to its destination . The SP is often referred to as the zip code in the postal system of protein trafficking. , Proteins are trafficked from the ribosome to the organelles or cell membrane with the help of either signal response particles (SRPs) or chaperon proteins. , SP plays an important role, from binding with the SRP to trafficking proteins to the endoplasmic reticulum (ER). A SP contains 13–36 amino acid residues and possesses a tripartite structure with a central hydrophobic h-region, a positively charged n-region, and a c-region, which adopts an extended β-conformation to facilitate recognition by the signal peptidase.…”

“…15 The SP is often referred to as the zip code in the postal system of protein trafficking. 16,17 Proteins are trafficked from the ribosome to the organelles or cell membrane with the help of either signal response particles (SRPs) or chaperon proteins. 18,19 SP plays an important role, from binding with the SRP to trafficking proteins to the endoplasmic reticulum (ER).…”

Non-Specific Signal Peptidase Processing of Extracellular Proteins in Staphylococcus aureus N315

“…The proteins that are to be exported outside the cell contain N-terminal leader peptide sequences, which are key determinants for particular secretory pathways [ 8 , 9 , 10 ]. Gram-positive bacteria, including S. aureus , have at least six different secretion pathways, consisting of the general secretory pathway (Sec-type), the twin-arginine (Tat) pathway, the pseudopilin-like (Com) pathway, ESAT-6, bacteriocin, and the Holins leader peptide pathway [ 11 , 12 , 13 , 14 ].…”