|
- picture Vesicle production, transport and fusion
|
| bet | 11/13 | | Sana | 16.05.2024 | | Hajmi | 1,48 Mb. | | #237391 |
Bog'liq Structure and function of biological membranes.2.3 3- picture Vesicle production, transport and fusion.
The formation and fusing of vesicles are energetically demanding, as these processes require the stable bilayer to be broken in order to pinch off a new vesicle, and then fused with a different membrane. Both energy and specialized protein machinery are required to overcome this energy barrier.
Once the vesicle has budded, travelled through the cytosol and reached its destination, it must fuse with its receptor membrane. Again this is an energetically unfavourable process, and protein machinery has to be utilized in order to allow the fusion of two bilayers. SNARE proteins are central to the process of vesicle fusion. Vesicles carry v-SNAREs that bind to specific t-SNAREs on the target membranes. Not only does this confer specificity in the targeting of vesicles, but also the SNAREs facilitate membrane fusion on arrival of the vesicle. The interacting v-SNAREs and t-SNAREs form a four-helix bundle at the interface between the two membranes, consisting of three helices from the t-SNARE and one helix from the v-SNARE. This stable interaction is thought to provide the free energy necessary to enable the two membranes to become very close and fuse. As the two bilayers become closer, the lipids in the two outer leaflets can come into contact with one another, thereby increasing the hydrophobic nature of the site and enabling the membranes to join, and overcoming the energy barrier. The transmembrane domains of the SNAREs are also believed to be involved in membrane fusion, as when they are replaced by lipids experimentally, fusion does not occur. Upon fusion, the cargo enters the target compartment, and the lipids and membrane proteins that formed the vesicle diffuse into the target membrane.
Determining the mechanisms of membrane budding is important for understanding how viruses such as the human immunodeficiency virus (HIV) produce new viral particles. Unlike the budding in the secretory pathway described earlier, HIV particles bud away from the cytoplasm, into the extracellular space. This viral budding occurs in the same orientation as the budding that occurs within endosomes. The proteins which enable this budding are referred to as endosomal sorting complexes required for transport (ESCRTs). HIV ‘hijacks’ the ESCRT machinery to enable it to bud from the plasma membrane, out of the cytoplasm and into the extracellular space. Interactions between HIV proteins and ESCRT proteins recruit the host cell ESCRT machinery to the budding vesicle, allowing membrane scission and vesicle release. Other viruses can bud without assistance from the ESCRTs, and it is thought that HIV may also be able to bud in an ESCRT-independent manner. Understanding more about these membrane budding and scission events is crucial to elucidating how viruses proliferate and how we can inhibit processes by means of drug interventions.
|
| |
