A ‘pocket’ in the protein called cyclin B plays a critical role in ensuring that cell division occurs in the right sequence.
Cell division is essential for life. All living organisms, ranging from the tiniest yeast to complex humans, rely on the continuous replication of cells. Various mechanisms are in place to ensure these steps are executed in the correct order, preventing errors that could lead to issues like tumors. A team of researchers at the University of Konstanz, led by biologist Thomas Mayer, has identified a control mechanism linked to a specific binding area, or pocket, that assists B-type cyclins in attaching to substrates, thereby influencing the orderly progression of cell division activities.
The importance of correct sequencing
In the process of cell division, it is crucial for all steps to consistently happen in the exact same manner. Any deviation can result in malformations. Depending on the cells involved and the specific step, this could potentially lead to tumor formation or infertility. “In two studies, we investigated if the docking site on cyclin B, essentially a type of pocket, affects the proper sequence of events and its implications,” Mayer explains. “By intentionally altering this docking site, we determined that malformations arise during cell division when the pocket loses its configuration and can no longer attach to the substrate.”
This is linked to the collaboration between cyclins and a type of enzyme called kinases. Kinases are critical for the phosphorylation of amino acids in substrates, an essential part of the cell division process. Another key aspect influencing phosphorylation is the surrounding environment of the amino acids. If kinases are free-floating, they typically phosphorylate amino acids in optimal conditions. “However, when cyclin B binds to substrates through its pocket, it effectively brings the kinase closer to these substrates. This allows the kinase to also phosphorylate amino acids that may not be in ideal conditions,” explains Thomas Mayer. “Essentially, the pocket on cyclin B acts like a Velcro fastener that links the kinase and the substrate, which in turn helps facilitate the proper sequence of events during cell division,” he adds.
Absence of the pocket disrupts cell division
The research team, under Thomas Mayer’s leadership, has now illustrated this mechanism in two B-type cyclins. Cyclin B1 is significant during mitosis, a form of cell division. The researchers noted how cyclin B1 binds to substrates using its pocket, which subsequently impacts the kinase’s behavior. “As a verification, we examined the consequences of having a missing or improperly functioning pocket on cyclin B1. By mutating the pocket, we observed that mitosis did not proceed as intended,” Mayer states. This can lead to errors in chromosome separation, causing mitosis to occur too slowly or incorrectly, which may trigger tumor formation.
Cyclin B3, in contrast, is vital for meiosis, another cell division type. It guarantees that meiotic division occurs correctly, resulting in the development of a healthy egg cell. In the study, researchers intentionally disrupted the process by altering the cyclin B3 pocket, which prevented the maturation of the egg cell. “A defective pocket on cyclin B3 can thus be a contributing factor to infertility,” concludes Mayer.
“While it was previously known that such pockets exist on B-type cyclins, we have now been able to clearly demonstrate their importance in maintaining the proper sequence of events during cell division,” Mayer states. This research paves the way for further studies aimed at enhancing our understanding of cellular processes and improving targeted treatments for various diseases.
