UC Berkeley researchers improve understanding of gateway to nucleus

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The mysterious processes that determine what goes in and out of the nucleus of a cell are now better understood than ever, thanks to work conducted by UC Berkeley researchers.

In a study published Friday, a team of researchers led by Mohammad Mofrad, a campus professor in the departments of mechanical engineering and bioengineering, detailed the investigation of the nuclear pore complex , or NPC, an intricate molecular machine that acts as a gateway to a cell’s nucleus and oversees the entrance and exit of more than 1,000 molecular cargos per second.

A single human cell may have as many as 2,000 NPCs, and although their significance in effecting disease is widely recognized in the scientific community, there is little consensus regarding how they work.

In fall 2013, Mofrad and his team examined the physical structure of NPCs, hoping to gain insight into their molecular machinery through investigation of the amino acid sequences of their proteins — the building blocks of NPCs.

Mofrad’s lab examined more than 1,000 different NPC components in more than 200 different species and found that they maintained a fairly uniform protein structure, despite their different origins.

“We found that there is a very nice, evolutionarily conserved feature,” said Mohammad Soheilypour, another graduate student and co-author of the study.

The researchers found similarities at the ends of NPC structures, but the central regions contained disorganized amino acid sequences. Known as “FG Nups,” these seemingly disorganized amino acids are “the key players in nuclear transport,” according to Mohaddeseh Peyro, a UC Berkeley graduate student and co-author of the study.

Despite their apparent disorganization, many FG Nups are either charged or polarized, creating “like-charge regions” in the amino acid sequences of NPCs. Positive like-charge regions prepare the NPC for negatively charged cargo, making the process of regulating cargo transport extremely efficient.

The FG Nups are significant, in part, because they are particularly prone to mutations, which can inhibit the function of NPCs, leading to risk of diseases such as cancer, nervous disorders and a host of viruses affecting the cell.

“When nuclear pores don’t work properly, it means that something will go wrong,” Soheilypour said.

But the work of Mofrad’s lab may contribute to efforts to stop things from going wrong.

“If we understand how the NPC works, maybe we could actually intervene and try to address some of these diseases,” Mofrad said.

An improved understanding of NPCs could benefit other scientific fields, too.

“Nothing in nature works as elegantly as the NPC,” Mofrad said, referring to the molecular machinery’s ability to rapidly yet selectively control the movement of cargo in and out of the nucleus.

Successfully mimicking this process of rapid filtration could prove invaluable in a variety of scientific exploits.

Contact Maxwell Jenkins-Goetz at [email protected].