User:Elizabeth G. Aylesworth/Sandbox 1

You may include any references to papers as in: the use of JSmol in Proteopedia ^[1] or to the article describing Jmol ^[2] to the rescue.

History

Thus far, there are 723 different types of coronin proteins, and of these 723, only 614 have complete structure models. These proteins are then sorted into four types of proteins with type I and II being specific just to metazoan classes. Type III are for tandem while type IV contains coronins that fuse to villin. Along with the four types of coronin based on the organism the coronin is present in, there are also two subfamilies that consist of long coronin and short coronin. The long coronin do not have a coiled-coil structure and have two tandems in the core. The N-terminal also only has five amino acids. Short coronin has about less than 700 amino acids and a coiled-coil structure. Unlike the long coronin, the short coronin’s N-terminal consists twelve amino acids(11).

As part of the WD40-repeat protein suprafamily, coronin are expected to have at least a

repeated sequence of four WDs as well as a propeller. When the structure was determined, it was found that coronins have a repeated sequence of five, and instead of a five beta-propeller, it has a seven beta-propeller.

Three variants of coronin-1C have been identified in humans. This affects the region just before

the coiled-coil area of the coronin protein as well as the N-terminal being elongated compared to other coronin proteins. This protein, though complete structure has not been confirmed, does have oligomeric properties(11).

Dictyostelium discoideum was the first organism in which coronin was identified. Since that discovery in 1991, plants are the only eukaryotes that coronin has not been identified. There are 12 subfamilies, and half of them are found only in vertebrates (1.

Function

The function of coronin 1C can be seen in many parts of the cell. Coronin 1C helps the cell to migrate by “regulation the activation and subcellular location of RAC1” (2). Coronin 1C helps to organize the cytoskeleton, helps the proliferation of the cell, and helps form a lamellipodia. This protein "interacts with the non-alpha-helical amino-terminal domain of vimentin"(9). This helps to show how the coronin is an integrator of the filaments and microtubules. Coronin 1C is “localized to endosome membrane tubules and promotes recruitment of TMCC1, leading to recruitment of the endoplasmic reticulum to endosome tubules for fission” (2). Coronin 1C has a high ability to bind F-actin, which leads to depletion of the cell, lamellipodia. The amount of coronin 1C in a depleted cell is higher than any of the other coronins, which is why they believe there is a second binding site(6). Even though coronin 1C lacks a phosphorylation site, it still binds with the Arp 2/3 complex. The propeller of the coronin interacts with the open Arp 2/3 complex, which allows a conformation in shape to happen

Disease

Coronin 1C is seen in many different cancers. The promotor of coronin 1C binds to C-myc in lymphoma cells. The levels of coronin 1C are low in normal skin cells, but high in melanoma cells. It is used as a marker for hepatocellular carcinoma (HCC), but the expression is dependent on the Erk pathway. If coronin 1C is imbalanced, it could lead to a defect in the brain growth. This could also lead to brain diseases. Coronin 1C is high at the start of development and decreases as the brain develops. Coronin 1C is also found in brain tumors, but the levels depend on where the brain tumor is in the brain (3).

Relevance

Coronin 1C uses the Arp 2/3 complex with motility and phagocytosis. A deletion of the gene coding for coronin does not cause abnormal function of endocytosis, but it does interact abnormally with other genetic mutations. For this reason, coronin is an important protein for the proper function and form of the cytoskeleton. In other organisms coronin being either deleted completely or over or under produced can prove to affect endocytosis and phagocytosis negatively or be deadly (4).

Structural highlights

Coronin 1C is a part of proteins that are approximately 474 amino acids long. Coronin 1A has Asp452 on the 3 position, whereas Coronin 1C has Ser463. This allows the protein to be phosphorylated, which interferes with Arg461’-Glu466, thus leading to the loss of a coil. Another structural difference is that Coronin 1C has a Ser450 in a hexa-peptide, which is not found in other coronin proteins. This allows for another phosphorylation site for the protein. This, however, has not been shown to impact the protein function in significant ways (5).

There are three parts of coronin 1C: the propeller, unique segment, and coiled coil domain. The propeller binds with the F-actin. The coiled coil domain helps coronin 1C bind with Arp 2/3 complex and forms trimers and dimers. The unique segment is not fully understood. Coronin 1C is different because it also has a second actin binding site. Coronin 1C lacks the phosphorylation site but can still bind the complex (6). If the Coronin 1C is phosphorylated, then the protein moves throughout the cytoplasm, not reacting with the plasma membrane. Coronin 1C is eight residues longer than 1A. If the coiled coil domain is deleted in coronin 1C, it prevents the creation of a bond to the plasma membrane (7). It is not a transmembrane protein and instead only binds to the membrane with the cytoskeleton through interaction with cholesterol (8).

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