Scientists Discover How Nuclear Pores Protect Genetic Material

Scientists at the Max Planck Institute of Biophysics and Johannes Gutenberg University Mainz have discovered how nuclear pores preserve genetic material by forming a permeable barrier that blocks pathogens. Nuclear pores act as guardians of the genome, allowing necessary substances to pass through while barring entry to harmful pathogens. Researchers have known that the proteins that extend from the scaffold of the nuclear pore resemble spaghetti, but until now they did not know how the proteins were arranged or how they functioned to protect the genome.

For the study, published in Nature, the team, led by Gerhard Hummer and Edward Lemke, used a combination of synthetic biology, multidimensional fluorescence microscopy, and computer-based simulations to study intrinsically disordered proteins (IDPs) in nuclear pores. IDPs lack a defined 3D structure and are continuously moving, making it difficult for scientists to determine their three-dimensional architecture and function. However, the team used precision tools to mark the spaghetti-like proteins with fluorescent dyes, allowing them to deduce how the proteins must be arranged. They then used molecular dynamics simulations to calculate how the IDPs were spatially organized in the pore, how they interacted with each other, and how they moved.

The researchers found that the tentacles in the transport pore interacted with each other and with the cargo, moving continuously like spaghetti in boiling water. This interaction forms a shield of wiggly, spaghetti-like molecules that are permeable for important cellular factors but block pathogens. IDPs are found in almost all species and carry the risk of forming aggregates during the aging process, leading to neurodegenerative diseases such as Alzheimer's.

The scientists' discovery has important implications for understanding how the nuclear pore functions and how it can be improved. By identifying errors in the transport or blocking of cargo, scientists can develop new drugs or vaccines to prevent viral infections and promote healthy aging. IDPs, despite being error-prone, are indispensable for certain cellular functions, and by studying their function in more detail, researchers aim to develop therapies to combat aging-related diseases.