Nuclear Pore Complex: Cell Nucleus Is Crucial to Healthy Aging [Study]

The nuclear pores have a dynamic network to keep us safe and healthy. It serves as a barrier, obstructing dangerous intruders like viruses and other harmful pathogens from passing.

Nuclear Pore Complex

Tiny holes within the cell nucleus are essential for healthy aging since they protect and preserve the DNA. The Synthetic Biophysics of Protein Disorder Group at Johannes Gutenberg University Mainz and the Department of Theoretical Biophysics at the Max Planck Institute of Biophysics in Frankfurt am Main, Germany, have literally filled a gap in our knowledge of the composition and operation of these nuclear pores.

The researchers' findings clarified the behavior of inherently disordered proteins found in the pore's center. They discovered that these proteins combine to create a flexible, spaghetti-like barrier that prevents viruses and other harmful pathogens from entering while allowing vital cellular components to get through.

Human cells enclose their genetic material in the nuclear membrane-shielded nucleus of the cell. The nucleus needs to be able to communicate with the remainder of the cell to exchange crucial messenger molecules, metabolites, or proteins. As a result, the nuclear membrane has roughly 2000 pores containing about 1000 proteins, SciTechDaily reported.

These nuclear pores serve as guardians of the genome, allowing only substances needed for cell control to pass while preventing the entry of pathogens or other substances that could damage DNA. For decades, researchers have been enthralled by the three-dimensional structure and function of these nuclear pores. Therefore, the nuclear pores can be compared to molecular doormen that inspect thousands of guests per second and only those with entrance tickets are allowed to enter.

How do the nuclear pores do such a difficult task? The center aperture is deep, and about 300 proteins connected to the pore scaffold extend outward like tentacles. The arrangement of these tentacles and how they deter intrusion were unknown until today. This is due to these proteins' intrinsic chaos and lack of a clear three-dimensional structure. They move continuously and with flexibility, much like spaghetti in boiling water.

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Researchers Use Modern Precision Tools to Mark Proteins

It is challenging for scientists to understand the three-dimensional architecture and function of intrinsically disordered proteins (IDPs), because they continually change their shape. The majority of experimental methods that scientists employ to scan proteins only function with a known 3D structure. Since the organization of the IDPs in the opening could not be determined, the core region of the nuclear pore has only been depicted as a hole thus far.

Using a novel synthesis of synthetic biology, multidimensional fluorescence microscopy, and computer-based simulations, the team headed by Gerhard Hummer, Director at the Max Planck Institute of Biophysics, and Edward Lemke, Professor of Synthetic Biophysics at Johannes Gutenberg University Mainz and Adjunct Director at the Institute of Molecular Biology Mainz, has now studied nuclear pore IDPs in living cells.

According to Lemke, they marked various locations on the spaghetti-like proteins with fluorescent dyes that they stimulated with light and viewed under a microscope using modern precision instruments. They were able to determine how the proteins must be organized based on the glow patterns and duration.

To determine how the IDPs are spatially arranged in the pore, how they interact with one another, and how they migrate, Hummer said they used molecular dynamics simulations. They were able to see the entrance to the human cells' command center for the first time.

Hummer claimed that figuring out how pores move or obstruct cargo will make it easier to spot mistakes. After all, despite the barrier, some viruses are nevertheless able to access the cell nucleus.

With their combination of techniques, Lemke said they can now investigate IDPs in greater depth to see why they are essential for some cellular processes despite being error-prone. IDPs are indeed present in practically all animals, despite the possibility that they could aggregate as they age and cause neurological disorders like Alzheimer's.

The study was published in the journal Nature.