Calreticulin (CRT) is a multifunctional protein with a highly conserved structure across different species. It primarily resides in the endoplasmic reticulum (ER), but it can also be found in other cellular locations. CRT’s structure and functions can be broken down as follows:
Structure: CRT is composed of three distinct domains:
- N-Terminal Domain (N-Domain): This region contains a signal sequence that targets CRT to the endoplasmic reticulum. It is also rich in highly conserved amino acids and is associated with chaperone functions, as it interacts with other proteins.
- P-Domain (Proline-Rich Domain): This central domain contains a high-affinity calcium-binding site, which allows CRT to bind and regulate calcium ions. Additionally, it features a lectin-like chaperone site, indicating its role in protein folding and interactions with glycoproteins.
- C-Domain (Carboxyl Domain): The C-Domain is rich in acidic amino acids, providing CRT with a high capacity for binding calcium ions. This domain also contains a KDEL signal, which serves as a retention signal for proteins within the endoplasmic reticulum.
Functions:
- Chaperone Activity: CRT serves as a molecular chaperone, aiding in the proper folding of proteins. When proteins are synthesized in the ribosomes and enter the endoplasmic reticulum, CRT can interact with them, assisting in the folding process. It helps proteins attain their correct three-dimensional structures, ensuring they function correctly. If a protein cannot fold properly, CRT can provide additional chances for it to achieve the correct conformation.
- Calcium Regulation: CRT plays a vital role in regulating intracellular calcium levels. It acts as a calcium buffer and sensor within the endoplasmic reticulum lumen. When cells require calcium for specific functions, CRT can release stored calcium, contributing to various cellular processes, including muscle contraction, signal transduction, and cell homeostasis.
- Cell Surface and Extracellular Functions: CRT is not limited to the endoplasmic reticulum but can also be found on the cell surface and in the extracellular matrix. In these locations, CRT participates in diverse cellular processes, such as signaling, regulation of gene expression, cell adhesion, apoptosis (programmed cell death), wound healing, cancer cell removal, and autoimmunity.
- Role in Parasite Infections: CRT has been identified in various parasites, and it can serve different functions, depending on the parasite’s species. For example, in Taenia solium tapeworms, CRT plays a role in egg development, making it a potential target for vaccination to interfere with parasite growth.
In summary, calreticulin is a highly versatile protein with a well-defined structure and numerous functions. Its chaperone activity ensures proper protein folding, while its calcium regulation helps maintain cellular homeostasis. Additionally, CRT is involved in a wide range of cellular processes, and its functions can vary depending on the cellular context and organism in which it is found.