User:Davi de Souza/Sandbox 1

Structure

Aerolysin proprotein is a protein that consists of 4 domains:

Domains 1 and 2 are responsible for binding to N-glycosylated phosphatidylinositol (GPI) proteins, which are present in the membranes of eukaryotic cells. Domain 1 binds to specific sugar modifications found on the GPI receptor, while domain 2 directly binds to the glycan core located in the central portion of GPI proteins. Therefore, both domain 1 and domain 2 are involved in anchoring the aerolysin proprotein to the target cell membrane.

Domain 3 is composed of a five-stranded beta sheet and a pre-stem loop, which are important for the insertion and anchoring of the protein into the cell membrane.

Domain 4 is an extension of the beta sheet from domain 3, but it is opened by the C-terminal peptide (CTP), forming a twisted double-fold in the beta sheet. This conformational change induced by the CTP propeptide allows the protein to fold into its soluble form. When the CTP is cleaved from the main body of the protein, the proaerolisin oligomerizes into a heptameric ring on the target cell membrane, forming a pore.

During proaerolisin oligomerization, domain 1 undergoes rotation, allowing all receptor binding sites to position themselves correctly relative to the target membrane. Domains 2 and 3 remain largely unchanged. On the other hand, domain 4, after cleavage of the CTP propeptide, undergoes rearrangement of the beta sheets, forming a beta sandwich. In the core of this sandwich, hydrophobic residues are internalized. Additionally, domain 4 rotates relative to domain 3, enabling hydrogen bonding between the beta sandwiches of two monomers, promoting the oligomerization of aerolysin.