Table of Contents
Nature has it that living organisms are made up of cells. From the smallest microorganisms such as bacteria, algae, fungi, and protozoan which are classified as unicellular to complex organisms such as plants and animals which are referred to as being multicellular. They are all made up of cells. Cells form the simplest structural and functional units for organisms. Cells have similar semi cellular components which include acids, proteins, carbohydrates, and lipids to ensure that they function properly. These components facilitate life and replication among the cells and ensure proper functioning of the cells. They also provide energy to the cell to boost their performance. Apart from being the building blocks for living organisms, cells are also fundamental for the continuation of life in living organisms. This is because they facilitate the passing of genetic materials which contain hereditary information from the parent organism to the next generation. The process of replication and duplication of cells to facilitate the transmission of genetic materials from the parent to the child organism is facilitated by invisible molecules known as the chromosomes. Chromosomes play a very important role in the cell division where parent cells are divided, and characteristics passed to the daughter cells. This is because it ensures that all the necessary hereditary information are passed from the parent cell to the daughter cell. The functioning of a chromosome is dependent on its structure. It is made up of the two arms which are referred to as the p-arm and the q-arm to distinguish them. The p-arm of a chromosome is shorter than the q-arm. The two arms are referred to as sister chromatids. Apart from the two sister chromatids, a chromosome also has microtubules which are hollow tubes made of protein and are utilized during the process of cell division. These microtubules play the role o moving chromosomes to the opposite sides during the process of mitosis. The microtubules are organized by structures known as the centrosomes (Sluder, 1996). This thesis examines the molecular structure of the most important part of the chromosome; the centrosomes and how it is important in the structure of a chromosome.
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Centrosomes are very important structures during the process of cell division as they assist in organizing microtubules to create the structure of the cell. The structure is grouped based on their different roles and the materials they are responsible for binding. Centrosomes also the role of regulating the stages involved in the cell division process. The roles of centrosomes in cell division process were discovered and discovered by Edouard Van Beneden and Theodor Boveri in 1883 and 1888 respectively. All the DNA structures which have centrosomes usually form if they have the given characteristics. They are often characterized to be small in size but with more complexity. The sequences for centrosomes are dependent on the presence of the necessary DNA in various cell regions. However, they can still form DNA sequences in other non-specified regions (Fu et al., 2015). Apart from acting as a structure which organizes microtubules, the centrosomes also play a very important role in information processing for other structures of the chromosome during the process of cell division. Some of the structures dependant on the centrosomes for their formation includes the mitotic spindle and other structure responsible for polarity and the locomotion of the cell. Due to its major role in the organization of the structure of the chromosome, the centrosome is referred to as the microtubule organizing center (MTOC) (Sluder, 1996).
Due to its major role in the formation of the chromosome structure, a centrosome has attracted much attention from biologist to examine its structure both molecular and physical structure. However, there have been various challenges in the process of studying the physical and molecular structure of the centrosome. The main challenge in that, due to its small size and the invisibility which makes it is difficult to obtain adequate information about its molecular structure. This has been mainly contributed by the fact that the components which make up the structure of the centrosome have no visible boundaries unlike other components of a cell. However, based on the available studies done on the structure of the centrosome, there are various descriptions about the molecular and physical structure of the centrosome. This essay will, therefore, specifically examine the molecular structure of the centrosome (Parkinson et al., 2006).
The structure of a centrosome as observed through powerful electron microscope appears to be made up of materials known as the centrioles. The centrioles occur in a pair and are surrounded by a substance known as the centrosome matrix. The discovery of the centrioles and other types of proteins which constitute the structure of the centrosome has been a good progress towards obtaining the molecular and the overall structure of the centrosome. Some of the proteins which have been discovered to play a very important role in the molecular structure of the centrosome include the α and the β tubulins. Apart from the two proteins, there are other structures which have also been discovered to important in the molecular structure of the centrosome. The ninein is a very important component in the formation of the centrosome as well. The component is formed through a cloning process of another component of the DNA known as the cDNA. The structure of the ninein is made up of layers of proteins which include myosin, lamin, and kinesin (Bouckson-Castaing et al., 1996). These proteins are bound separately to form domains that make up the structure of the ninein. Some of the common domains of ninein include EF-hand-like domain and the leucine zipper domains. The EF-hand-like region is characterized with ammonia ions and has similarities with the calmodulin and various parts of the human body containing calcium ions. This domain of proteins which make up the ninein has about 30 amino acids which occur in various sequences such as loop, helix, and loop. Some parts of this domain are compatible with water while others do not. On the other hand, the leucine zipper domains are divided into four subdomains which are referred to as LZ1, LZ2, LZ3, and LZ4. Out of the four subdomains, LZ4is the largest and contains regions with isoleucine instead of leucine. Unlike other components, ninein is always present in the structure of the centrosome during all the cell division process. Generally, ninein is considered an acidic protein made up of amino acids which are the building blocks of any protein. The analysis done on the ninein has also shown that it lacks immune substances. This means that the substance is very weak regarding defense and can be overcome easily. The discovery of the ninein has been great progress towards examining the structure of the centrosome (Bouckson-Castaing et al., 1996).
Apart from the ninein, another major component of the molecular structure of the centrosome is the polo-like kinase one also referred to as plk1. This component which is also part of the processes in mitosis stage of interphase is contained from the prokaryotic organisms such as fungi up to the eukaryotic organisms such as animals. Kinase 1 is considered one of the most important components of the centrosome despite being present at only a few stages of the mitosis process. This is because it is involved in the formation of some of the key components of the chromosome. Some of the key roles of this component in the centrosome include its involvement in the arrangement of the mitotic spindle in the chromosome. It also plays a role in regulating cycle-dependent kinases (CDK) and cyclin complex. Other substances regulated by this component include anaphase-promoting complex (APC) which is also referred to as the cyclosome and cytokinesis (Sluder, 1996). The process of mitotic exit is also much depended on this substance for control. Another role of the plk1 is to remove cohesion of the chromatin during the interphase stage of the mitosis. Therefore, the polo-like kinase is involved in many roles during its presence in the centrosome. To facilitate its functionality and ensure efficiency in its role, plk1 has numerous components present in it. These components include the Cdc25C phosphate which is one of the major components of this structure. The anaphase-promoting complex/cyclosome often referred to as APC/C is also part of the substances contained in the structure apart from being controlled by the same structure. Cyclin B and SCC1 cohesin also make up the plk2 components. Finally, the cytokinesis group six to eight are part of the plk2 major components among many others. All the components have different roles during the process of mitosis to realize an efficient functioning of the plk2, centrosome and the chromosome in general (García-Álvarez, de Cárcer, Ibañez, Bragado-Nilsson, & Montoya, 2007).
The structure of the polo-like kinase is composed of domains as observed in the structure of the ninein. The N-terminal catalytic domain is the first domain component of the plk1. The main role of this domain is to facilitate the localization of the centrosome which can be done in absence substrate binding. It also primarily involved in the substrate recognition process. On the other hand, the C-terminal regulatory domain is the second type of domain for the plk1. Its main role is to react with the catalytic domain to provide molecular regulation of the protein kinase. It also facilitates the phosphorylation process of the plk1. Apart from the two domains, the plk1 structure is also made up of sequences referred to as the polo boxes or commonly the PB. The role of this component is only observed in plk1 and has a unique characteristic among the protein group. This characteristic facilitates the regulation process of substrates by the kinase. The polo boxes domain also plays the role of facilitating or controlling mitosis as it is part of the circuit that regulates the process. Specifically, the role of the polo-box domain of the plk1 in the regulatory circuit is to enhance the process of phosphorylation of the Cdc25C (Ohta et al., 2002). Due to this feature of the plk1 acts as an activator for components such as the Cdk1. The process of the activation of Cdk1 by the Plk1 is depended on the subsequent process of activation. Research has also described the polo-box domain of the Plk1 as a peptide found in various domains which are nonprotein. This finding associated polo box domain as a component of the Plk1 with centrosome localization and the process of substrate recognition. However, the integrity of the findings is questionable regarding the dependency of the centrosome localization on the polo-box domain of the plk1. This is because the N-terminal domain of the plk1 facilitates independent centrosome localization which does not rely on the substrate binding and phosphorylation which is facilitated by the polo-box domain. Furthermore, the localization process is also not determined by the substrate binding. Rather, a forward activation had done before the substrate binding triggers the process of localization (Parkinson et al., 2006).
The Cep135 is also one of the components which make up the molecular structure of centrosome mainly found in cells of eukaryotic organisms specifically the mammals. Their basic structure resembles a whorl-like particle which varies in size shape and level of production. Generally, the appearance of the Cep135 is novel coiled-coil protein. However, they have a similar structure of lines with equal length and density. It is protein in nature and is found in various kinds of organisms ranging from the prokaryotic to the eukaryotic. Same as ninein, Cep135 is also found in the molecular structure of the centrosome throughout the process of cell division. It is generally found in all the parts of the centrosome especially along the centrioles which are the main component of the centrosome. Its structure is made up materials which contain electrons (Bouckson-Castaing et al., 1996). This component is important in the role of the centrosome of formation of the mitotic spindles and the organization of the chromosome components during the interphase stage of the mitosis. It also plays a very important role in the arrangement of microtubules in the cells of eukaryotic organisms such as mammals. However, their functionality is dependent on various factors such as their level of production. Overproduction of the component could have impacts on the formation of microtubules found in mitotic spindles and the structure of the chromosome in the interphase stage. The structure of the Cep135 is also characterized by amino acids which tend to be unique from the other molecules. The structure of this component is also characterized by the presence of cDNA clones. These clones are obtained from cDNA which is fragmented according to the difference in Cep135 sequence and structure. Thus, the cDNA clones can be classified into various categories based on the nature of the sequence alignment based on the size of the transcripts. Most of the clones differ mainly in regions where deletion occurred making them transitional (García-Álvarez et al., 2007). The Cep135 together with helix and coiled-coil make up major components of the molecular structure of the centrosome. Research has also shown that Cep135 is also divided into various domains. The role of these domains is to facilitate centrosome targeting hence influencing the molecular structure of centrosomes. The process of the formation of Cep135 in the centrosome involves the structure of the centrosome being associated with filaments which are estimated to be having a length of around 6-nm. These filaments are usually accompanied by particles which appear to be whorl-like. However, the whorl-like particles are not aligned together. The appearance of the Cep135 is in three dimensions and quite different from other structures which are also obtained from proteins. The size of the whorl produced during the formation of this structure is depended on the amount of proteins availed. At some instances, both the whorl and the filaments of the Cep135 are formed on the centrosome. After some time, the whorl increases in size and emerge outside the centrosome especially if it has limited space to handle the components (Sluder, 1996). Surprisingly the process in which the Cep135 is associated with the centrosome is completely unknown. However further research have indicated that probably this component of the centrosome is derived from the large protein complex. If that is the case, then this is a clear indication that the localization of Cep135 is done in the cetrosome together with other large protein complex. Basically, the components that are obtained after the fragmentation of the Cep135 component after the process of localization include the helices which are extensive in nature, the leucine zipper and the ammonium terminal. This indicates that the process through which proteins are availed to the centrosome is done through a process which involves other coiled-coil proteins which are also present in the centrosome (García-Álvarez et al., 2007).
Further studies have proposed the probability of the existence of diverse functions of the Cep135 as one of the molecular components of the centrosome. This is due to its the unique characteristic of having fibrous aggregates. This feature enables the composition of the centrosome to have the ability to ensure there is necessary organization and functioning of the pericentriolar materials. To perform this role, the Cep135 regulates the release of centrosome from the association which tight in the nucleus. Furthermore, when Cep135 is availed in excess, it facilitates the maintainance of the structure of the pericentriolar material. Hence Cep135 plays a very important role in the molecular structure of centrosomes (Parkinson et al., 2006).
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The Nek2 kinase is a type of kinase which also makes up part of the molecular structure of the centrosome. It is classified as part of the NIMA kinase which is a group of the related kinase whose main role is to facilitate the process of mitotic entry. Another group of NIMA kinase is also responsible for the mutations which lead to cells that do not undergo the process of mitosis. These functions by the group of the kinase are mainly found in fungi and other prokaryotic organisms. This is where they are involved in the process of chromosome segregation and the exit of the mitosis process. On the other hand, eukaryotic organisms, contain Nek2 kinase within their genes. All eukaryotic organisms in exception of the human beings have three types of adjacent domains which are the N-terminal kinase domain, and the C-terminal domain which serves the role of regulation due to their non-catalytic. These domains indicate their differences that exist due to different roles in enhancing the molecular structure of the centrosomes. In human beings, Nek2 has a unique characteristic of being the only protein that has similarities with kinases found fungal (Sluder, 1996). The two have about 50% similarity index in their amino acid sequences. Ideally, Nek2 is also one of the most important components in the formation and the functionality of the centrosome. After its localization into the centrosome, the Nek2 kinase serves the role of spindle formation which occurs during the period of mitosis. Nek2 is also responsible for spindle pole formation and separation which facilitates the formation of the structure of a cell. The component is also important in the centralizing microtubules and assembling the spindles in a cell. Apart from its numerous roles in the centrosome, the kinase is also responsible for chromatin condensation and spindle separation. The structure of nek2 shows the presence of a fold which is attributed to the bilobal kinase. They also have to be activated through the process of phosphorylation for them to be fully functional (Parkinson et al., 2006).
The structure of Nek2 indicates the presence of an inhibitor which is found at ATP region and is attached to the structure by strong hydrogen bonds. Some bonds are also formed in the indole oxygen and the pyrrole ring whose role is to ensure proper stabilization of the ring extension. The structure of Nek2 has also been associated with a component known as SU1652 which is a compound (Rellos et al., 2007). The role of this compound is to act as a potent and at the same time a receptor of the ATP- competitive kinase. It is also associated with other components of the cell such as the vascular endothelial, the fibroblast, and EFR among others. SU11652 compound serves as an inhibitor which stimulates the growth in the various components of the centrosome. It has also been linked with serine which is a protein kinase also related to another compound known as the tumorigenesis (Parkinson et al., 2006). One of the unique features of the Nek2 among all the components of the centrosome is that it is associated with various types of inhibitors which serve various roles. One of the most common inhibitors associated with Nek2 is the type I scaffolds inhibitor whose primary role is to promote the stabilization of the DFG-out conformation. Another common type of inhibitor associated with Nek2 is the type II which is found only in conditions where inactive DFG-out conformation is supported. Inactive conformation is mainly supported by the structure of the Nek2 together with SU11652 compound. The various inhibitors and organelles in Nek2 play a very important role in the molecular structure of centrosome (Sluder, 1996).
In conclusion, a centrosome is a very complex structure of a cell. This is because it has numerous components and organelles that make up its molecular and physical structure. Various challenges have been encountered to study the molecular structure of a centrosome. This has been due to its characteristic of having no visible boundaries within various organelles. However, the limited information obtained from the structure of the centrosome has been important in describing its molecular and physical structure. According, to studies obtained from the study of centrosome it has been established to have various components ranging from proteins, catalysts and non-catalysts, ions, amino acids, substrates and many other substances. The role of the various substances present in the molecular structure of the centrosome has been to facilitate the functionality of the centrosome in the process of cell division.
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- Fu, J., Hagan, I. M., & Glover, D. M. (2015). The centrosome and its duplication cycle. Cold Spring Harbor Perspectives in Biology, 7(2), a015800.
- García-Álvarez, B., de Cárcer, G., Ibañez, S., Bragado-Nilsson, E., & Montoya, G. (2007). Molecular and structural basis of polo-like kinase 1 substrate recognition: Implications in centrosomal localization. Proceedings of the National Academy of Sciences, 104(9), 3107–3112.
- Ohta, T., Essner, R., Ryu, J.-H., Palazzo, R. E., Uetake, Y., & Kuriyama, R. (2002). Characterization of Cep135, a novel coiled-coil centrosomal protein involved in microtubule organization in mammalian cells. J Cell Biol, 156(1), 87–100.
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