Protein targeting or protein sorting is the biological mechanism by which proteins are transported to their appropriate destinations within or outside the cell. Proteins can be targeted to the inner space of an organelle, different intracellular membranes, the plasma membrane, or to the exterior of the cell via secretion. Information contained in the protein itself directs this delivery process. Correct sorting is crucial for the cell; errors or dysfunction in sorting have been linked to multiple diseases.
The signal recognition particle (SRP) is an abundant, cytosolic, universally conserved ribonucleoprotein that recognizes and targets specific proteins to the endoplasmic reticulum in eukaryotes and the plasma membrane in prokaryotes.
A signal peptide is a short peptide present at the N-terminus of most newly synthesized proteins that are destined toward the secretory pathway. These proteins include those that reside either inside certain organelles, secreted from the cell, or inserted into most cellular membranes. Although most type I membrane-bound proteins have signal peptides, the majority of type II and multi-spanning membrane-bound proteins are targeted to the secretory pathway by their first transmembrane domain, which biochemically resembles a signal sequence except that it is not cleaved. They are a kind of target peptide.
The translocon is a complex of proteins associated with the translocation of polypeptides across membranes. In eukaryotes the term translocon most commonly refers to the complex that transports nascent polypeptides with a targeting signal sequence into the interior space of the endoplasmic reticulum (ER) from the cytosol. This translocation process requires the protein to cross a hydrophobic lipid bilayer. The same complex is also used to integrate nascent proteins into the membrane itself. In prokaryotes, a similar protein complex transports polypeptides across the (inner) plasma membrane or integrates membrane proteins. In either case, the protein complex are formed from Sec proteins, with the heterotrimeric Sec61 being the channel. In prokaryotes, the homologous channel complex is known as SecYEG.
A topogenic sequence is a collective term used for a peptide sequence present at nascent proteins essential for their insertion and orienting in cellular membranes. The sequences are also used to translocate proteins across various intracellular membranes, and ensure they are transported to the correct organelle after synthesis. The position of the sequence may be at the end, e.g. N-terminal signal sequence, or in mid parts of the nascent protein, e.g. stop-transfer anchor sequences and signal-anchor sequences. If the sequence is at the end of the polypeptide, it is cleaved off after entering the ER-lumen by a signal peptidase, and subsequently degraded.
COPI is a coatomer, a protein complex that coats vesicles transporting proteins from the cis end of the Golgi complex back to the rough endoplasmic reticulum (ER), where they were originally synthesized, and between Golgi compartments. This type of transport is retrograde transport, in contrast to the anterograde transport associated with the COPII protein. The name "COPI" refers to the specific coat protein complex that initiates the budding process on the cis-Golgi membrane. The coat consists of large protein subcomplexes that are made of seven different protein subunits, namely α, β, β', γ, δ, ε and ζ.
In cell biology, microsomes are heterogeneous vesicle-like artifacts re-formed from pieces of the endoplasmic reticulum (ER) when eukaryotic cells are broken-up in the laboratory; microsomes are not present in healthy, living cells.
Peter Walter is a German-American molecular biologist and biochemist and is Director of the Bay Area Institute of Science at Altos Labs, Professor at the University of California, San Francisco (UCSF). He was a Howard Hughes Medical Institute (HHMI) Investigator until 2022.
In molecular biology, the Signal Peptide Peptidase (SPP) is a type of protein that specifically cleaves parts of other proteins. It is an intramembrane aspartyl protease with the conserved active site motifs 'YD' and 'GxGD' in adjacent transmembrane domains (TMDs). Its sequences is highly conserved in different vertebrate species. SPP cleaves remnant signal peptides left behind in membrane by the action of signal peptidase and also plays key roles in immune surveillance and the maturation of certain viral proteins.
Signal recognition particle (SRP) receptor, also called the docking protein, is a dimer composed of 2 different subunits that are associated exclusively with the rough ER in mammalian cells. Its main function is to identify the SRP units. SRP is a molecule that helps the ribosome-mRNA-polypeptide complexes to settle down on the membrane of the endoplasmic reticulum.
Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1).
A Disintegrin and metalloproteinase domain-containing protein 10, also known as ADAM10 or CDw156 or CD156c is a protein that in humans is encoded by the ADAM10 gene.
Syntaxin-5 is a protein that in humans is encoded by the STX5 gene.
Nuclear pore complex protein Nup133, or Nucleoporin Nup133, is a protein that in humans is encoded by the NUP133 gene.
Mitochondrial-processing peptidase subunit beta is an enzyme that in humans is encoded by the PMPCB gene. This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex.
Signal peptidase I is an enzyme. This enzyme catalyses the following chemical reaction
Mitochondrial processing peptidase is an enzyme complex found in mitochondria which cleaves signal sequences from mitochondrial proteins. In humans this complex is composed of two subunits encoded by the genes PMPCA, and PMPCB. The enzyme is also known as. This enzyme catalyses the following chemical reaction
KKXX and for some proteins XKXX is a target peptide motif located in the C terminus in the amino acid structure of a protein responsible for retrieval of endoplasmic reticulum (ER) membrane proteins to and from the Golgi apparatus. These ER membrane proteins are transmembrane proteins that are then embedded into the ER membrane after transport from the Golgi. This motif is exclusively cytoplasmic and interacts with the COPI protein complex to target the ER from the cis end of the Golgi apparatus by retrograde transport.
Metalloendopeptidase OMA1, mitochondrial is an enzyme that in humans is encoded by the OMA1 gene. OMA1 is a Zn2+-dependent metalloendopeptidase in the inner membrane of mitochondria. The OMA1 acronym was derived from overlapping proteolytic activity with m-AAA protease 1.
The peptide-loading complex (PLC) is a short-lived, multisubunit membrane protein complex that is located in the endoplasmic reticulum (ER). It orchestrates peptide translocation and selection by major histocompatibility complex class I (MHC-I) molecules. Stable peptide-MHC I complexes are released to the cell surface to promote T-cell response against malignant or infected cells. In turn, T-cells recognize the activated peptides, which could be immunogenic or non-immunogenic.
