Coronin-1A is a protein that in humans is encoded by the CORO1A gene. [5] [6] It has been implicated in both T-cell mediated immunity and mitochondrial apoptosis. In a recent genome-wide longevity study, its expression levels were found to be negatively associated both with age at the time of blood sample and the survival time after blood draw. [7]
The coronin protein family was discovered in 1991 by Eugenio L. Hostos. Hostos used a cytoskeletal preparation called the “contracted propeller” that efficiently helped with the purification of cytoskeletal proteins. This technique allowed him to precipitate actomyosin components together with the desired proteins. [8]
These protein were named Corona, which is the Latin word for crown, because of the crown-like shape that it forms when making contact with the surface of the cell. Coronin-1a has been the most researched one due to its complexity and intriguing structural components. After research, it was determined that coronin-1a serves as actin binding facilitator when reacted with K-glutamate. The anion K + and glutamate were used because of it similarity to the environment inside the cell, allowing coronin-1a to bind to F-actin.
Later on, the complementary DNA (cDNA) of coronin-1a was cloned in an expression library, this led to the conclusion that coronin-1a has very similar structure to the beta (β) subunits of the G proteins (Gβ). Therefore, it was established that coronin-1a has five WD motif repeats, and this repeats seven times forming a propeller like structure. [8]
In the cell, coronin-1a serves as an auxiliary to many cytoskeletal process that involve actin. It was concluded that coronin-1a is known to affect the “cytoskeletal reorganization” as well “actin dynamics” together with other protein. [8]
The coronin family is composed of twelve subfamilies which include: seven subfamilies that fall under vertebrates and five subfamilies that are composed of metazoans, fungi and amoeba.
The evolutionary coronin subfamilies have been grouped by its similarities and relationships between the different proteins. Coronin-1a (also referenced as CORO1A, Coronin 4 and CRN4) has been found in 19 vertebrates. [9]
Coronin-1a has been found in the cell cortex of macrophages, which are white blood cells, helping with a process called phagocytosis. The model on Figure 3 shows coronin-1a's involvement in macrophages. When the cell is at rest, Coronin-1a is spread out throughout the cytoplasm and the cell cortex. Therefore, when a pathogen enters the cell, Coronin-1a binds to phagosomal membrane making sure of the binding and activation of calcineurin, this resulting in a stop of fusion lysosomes with phagosomes. In other words, if coronin-1a is removed and calcineurin is inhibited then it allows the initiation of the fusion of phagosomes with lysosome and the killing of mycobacteria. [10]
The phylogenetic tree of the coronin family it is broad. The same way that coronin-1a helps with the reorganization of the cytoskeleton and dynamic activity with other proteins in vertebrates, Coronin can also be seen in non-vertebrates, for example in Toxoplasma gondii (also known as TgCor). [11]
Toxoplasma gondii coronin (TgCor) binds to F-actin and it accelerates the actin polymerization process. It also prevents incursions and exits. As well as every other coronin, TgCor is an actin binding protein, it delocalizes to the posterior side of invading parasites and blocks them from leaving. [11]
The structure of coronin-1A is made out of five WD repeats, and this motifs repeat seven time forming a propeller like structures.
The new ribbon visualization of the secondary structure of coronin-1a. In model A, is the front view of coronin-1a, the secondary structure allows you to clearly see the parallel beta sheets moving towards the bottom of the structure. Model B, is the side view of the protein which shows the turns and the coils between the beta sheets. From this pictures we are able to see that the alpha helix and helix strands are concentrated at the bottom of the protein. [12]
Coronin-1a was input into Database of Secondary Structure Program, where the Protein Data Bank database entered and a secondary structure panel is designed where one is clearly able to see the seven repeat that makes the propeller. Also, it displays the amino acid sequence of coronin-1a. The yellow arrows mean the beta strands, the purple loops are the turns, the black lines means empty meaning that there was no secondary structure assigned, the light pink is 3/10-helix is formed, royal blue line is a bend and finally the red helix signifies the alpha helices.
Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate Branchiostoma.
In mammalian cells, vinculin is a membrane-cytoskeletal protein in focal adhesion plaques that is involved in linkage of integrin adhesion molecules to the actin cytoskeleton. Vinculin is a cytoskeletal protein associated with cell-cell and cell-matrix junctions, where it is thought to function as one of several interacting proteins involved in anchoring F-actin to the membrane.
Sterol regulatory element-binding proteins (SREBPs) are transcription factors that bind to the sterol regulatory element DNA sequence TCACNCCAC. Mammalian SREBPs are encoded by the genes SREBF1 and SREBF2. SREBPs belong to the basic-helix-loop-helix leucine zipper class of transcription factors. Unactivated SREBPs are attached to the nuclear envelope and endoplasmic reticulum membranes. In cells with low levels of sterols, SREBPs are cleaved to a water-soluble N-terminal domain that is translocated to the nucleus. These activated SREBPs then bind to specific sterol regulatory element DNA sequences, thus upregulating the synthesis of enzymes involved in sterol biosynthesis. Sterols in turn inhibit the cleavage of SREBPs and therefore synthesis of additional sterols is reduced through a negative feed back loop.
Utrophin is a protein that in humans is encoded by the UTRN gene. The name is a short form for ubiquitous dystrophin.
Talin is a high-molecular-weight cytoskeletal protein concentrated at regions of cell–substratum contact and, in lymphocytes, at cell–cell contacts. Discovered in 1983 by Keith Burridge and colleagues, talin is a ubiquitous cytosolic protein that is found in high concentrations in focal adhesions. It is capable of linking integrins to the actin cytoskeleton either directly or indirectly by interacting with vinculin and α-actinin.
ROCK1 is a protein serine/threonine kinase also known as rho-associated, coiled-coil-containing protein kinase 1. Other common names are ROKβ and P160ROCK. ROCK1 is a major downstream effector of the small GTPase RhoA and is a regulator of the actomyosin cytoskeleton which promotes contractile force generation. ROCK1 plays a role in cancer and in particular cell motility, metastasis, and angiogenesis.
Filamin A, alpha (FLNA) is a protein that in humans is encoded by the FLNA gene.
LIM domain kinase 1 is an enzyme that in humans is encoded by the LIMK1 gene.
Actin, cytoplasmic 2, or gamma-actin is a protein that in humans is encoded by the ACTG1 gene. Gamma-actin is widely expressed in cellular cytoskeletons of many tissues; in adult striated muscle cells, gamma-actin is localized to Z-discs and costamere structures, which are responsible for force transduction and transmission in muscle cells. Mutations in ACTG1 have been associated with nonsyndromic hearing loss and Baraitser-Winter syndrome, as well as susceptibility of adolescent patients to vincristine toxicity.
The prokaryotic cytoskeleton is the collective name for all structural filaments in prokaryotes. It was once thought that prokaryotic cells did not possess cytoskeletons, but advances in visualization technology and structure determination led to the discovery of filaments in these cells in the early 1990s. Not only have analogues for all major cytoskeletal proteins in eukaryotes been found in prokaryotes, cytoskeletal proteins with no known eukaryotic homologues have also been discovered. Cytoskeletal elements play essential roles in cell division, protection, shape determination, and polarity determination in various prokaryotes.
Alpha-actinin-1 is a protein that in humans is encoded by the ACTN1 gene.
Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, also known as FGR, is a protein which in humans is encoded by the FGR gene.
S100 calcium-binding protein A11 (S100A11) is a protein that in humans is encoded by the S100A11 gene.
Anillin is a conserved protein implicated in cytoskeletal dynamics during cellularization and cytokinesis. The ANLN gene in humans and the scraps gene in Drosophila encode Anillin. In 1989, anillin was first isolated in embryos of Drosophila melanogaster. It was identified as an F-actin binding protein. Six years later, the anillin gene was cloned from cDNA originating from a Drosophila ovary. Staining with anti-anillin antibody showed the anillin localizes to the nucleus during interphase and to the contractile ring during cytokinesis. These observations agree with further research that found anillin in high concentrations near the cleavage furrow coinciding with RhoA, a key regulator of contractile ring formation.
TRIO and F-actin-binding protein is a protein that in humans is encoded by the TRIOBP gene.
Coronin-1C is a protein that in humans is encoded by the CORO1C gene.
Coronin is an actin binding protein which also interacts with microtubules and in some cell types is associated with phagocytosis. Coronin proteins are expressed in a large number of eukaryotic organisms from yeast to humans.
Coronin, actin binding protein, 1B also known as CORO1B is a protein which in humans is encoded by the CORO1B gene. Members of the coronin family, such as CORO1B, are WD repeat-containing actin-binding proteins that regulate cell motility.
The Actin assembly-inducing protein (ActA) is a protein encoded and used by Listeria monocytogenes to propel itself through a mammalian host cell. ActA is a bacterial surface protein comprising a membrane-spanning region. In a mammalian cell the bacterial ActA interacts with the Arp2/3 complex and actin monomers to induce actin polymerization on the bacterial surface generating an actin comet tail. The gene encoding ActA is named actA or prtB.
Coronin, actin binding protein, 2A is a protein that in humans is encoded by the CORO2A gene.
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