Read this and then tell me what you don't understand about it...
Most proteins that are secretory, membrane-bound, or reside in the endoplasmic reticulum (ER), golgi or endosomes use the co-translational translocation pathway. This process begins with the N-terminal signal peptide of the protein being recognized by a signal recognition particle (SRP) while the protein is still being synthesized on the ribosome. The synthesis pauses while the ribosome-protein complex is transferred to an SRP receptor on the ER in eukaryotes, and the plasma membrane in prokaryotes. There, the nascent protein is inserted into the translocon, a membrane-bound protein conducting channel composed of the Sec61 translocation complex in eukaryotes, and the homologous SecYEG complex in prokaryotes. In secretory proteins and type I transmembrane proteins, the signal sequence is immediately cleaved from the nascent polypeptide once it has been translocated into the membrane of the ER (eukaryotes) or plasma membrane (prokaryotes) by signal peptidase. The signal sequence of type II membrane proteins and some polytopic membrane proteins are not cleaved off and therefore are referred to as signal anchor sequences. Within the ER, the protein is first covered by a chaperone protein to protect it from the high concentration of other proteins in the ER, giving it time to fold correctly. Once folded, the protein is modified as needed (for example, by glycosylation), then transported to the Golgi for further processing and goes to its target organelles or is retained in the ER by various ER retention mechanisms.
The amino acid chain of transmembrane proteins, which often are transmembrane receptors, passes through a membrane one or several times. They are inserted into the membrane by translocation, until the process is interrupted by a stop-transfer sequence, also called a membrane anchor sequence. These complex membrane proteins are at the moment mostly understood using the same model of targeting that has been developed for secretory proteins. However, many complex multi-transmembrane proteins contain structural aspects that do not fit the model. Seven transmembrane G-protein coupled receptors (which represent about 5% of the genes in humans) mostly do not have an amino-terminal signal sequence. In contrast to secretory proteins, the first transmembrane domain acts as the first signal sequence, which targets them to the ER membrane. This also results in the translocation of the amino terminus of the protein into the ER membrane lumen. This would seem to break the rule of "co-translational" translocation which has always held for mammalian proteins targeted to the ER. This has been demonstrated with opsin with in vitro experiments. A great deal of the mechanics of transmembrane topology and folding remains to be elucidated.
The video is terrible, but it's an extra resource.
Quick Reply
