Transport vesicles bud from one compartment (donor) and fuse with another topologically equivalent (target) compartment. in the process, soluble components (red dots) are transferred from lumen to lumen. note that membrane is also transferred and that the original orientation of both proteins and lipids in the donor compartment membrane is preserved in the target compartment membrane. Thus, membrane proteins retain their asymmetric orientation, with the same domains always facing the cytosol.
transported proteins do not cross a membrane, vesicular transport can move proteins only between compartments that are topologically equiva lent (see Figure 12–4).
Each mode of protein transfer is usually guided by sorting signals in the transported protein, which are recognized by complementary sorting receptors. If a large protein is to be imported into the nucleus, for example, it must possess a sorting signal that receptor proteins recognize to guide it through the nuclear pore complex. If a protein is to be transferred directly across a membrane, it must possess a sorting signal that the translocator recognizes. Likewise, if a protein is to be loaded into a certain type of vesicle or retained in certain organelles, a complementary receptor in the appropriate membrane must recognize its sorting signal.
signal sequences and sorting receptors Direct proteins to the Correct Cell address
Most protein sorting signals involved in transmembrane transport reside in a stretch of amino acid sequence, typically 15–60 residues long. Such signal sequences are often found at the N-terminus of the polypeptide chain, and in many cases specialized signal peptidases remove the signal sequence from the finished protein once the sorting process is complete. Signal sequences can also be internal stretches of amino acids, which remain part of the protein. Such signals are used in gated transport into the nucleus. Sorting signals can also be composed of multiple internal amino acid sequences that form a specific three-dimensional arrangement of atoms on the protein’s surface; such signal patches are sometimes used for nuclear import and in vesicular transport.
Each signal sequence specifies a particular destination in the cell. Proteins destined for initial transfer to the ER usually have a signal sequence at their Nterminus that characteristically includes a sequence composed of about 5–10 hydrophobic amino acids. Many of these proteins will in turn pass from the ER to the Golgi apparatus, but those with a specific signal sequence of four amino acids at their C-terminus are recognized as ER residents and are returned to the ER. Proteins destined for mitochondria have signal sequences of yet another type, in which positively charged amino acids alternate with hydrophobic ones. Finally, many proteins destined for peroxisomes have a signal sequence of three characteristic amino acids at their C-terminus.
Table 12–3 presents some specific signal sequences. Experiments in which the peptide is transferred from one protein to another by genetic engineering techniques have demonstrated the importance of each of these signal sequences for protein targeting. Placing the N-terminal ER signal sequence at the beginning of a cytosolic protein, for example, redirects the protein to the ER; removing or mutating the signal sequence of an ER protein causes its retention in the cytosol. Signal sequences are therefore both necessary and sufficient for protein targeting. Even though their amino acid sequences can vary greatly, the signal sequences of proteins having the same destination are functionally interchangeable; physical properties, such as hydrophobicity, often seem to be more important in the signal-recognition process than the exact amino acid sequence.
Signal sequences are recognized by complementary sorting receptors that guide proteins to their appropriate destination, where the receptors unload their cargo. The receptors function catalytically: after completing one round of targeting, they return to their point of origin to be reused. Most sorting receptors budding vesicle with contents selected for recognize classes of proteins rather than an individual protein species. They can therefore be viewed as public transportation systems, dedicated to delivering numerous different components to their correct location in the cell.
most organelles Cannot Be Constructed De Novo: They require information in the organelle itself