Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New findings help explain speedy transported into and out of the cell's nucleus

21.09.2015

'Fuzzy' interaction makes it possible for the nuclear pore complex to rapidly and selectively move large molecules

A cell does everything it can to protect its nucleus, where precious genetic information is stored. That includes controlling the movement of molecules in and out using gateways called nuclear pore complexes (NPCs).


Because it lacks a predictable structure, an FG Nup (green), a component of the nuclear pore complex, can interact quickly with a transport factor (purple) bound to large cargo. This interaction makes selective and rapid transport into and out of the nucleus possible.

Credit: Laboratory of Cellular and Structural Biology at The Rockefeller University

Now, researchers at The Rockefeller University, Albert Einstein College of Medicine, and the New York Structural Biology Center have identified the molecular mechanism that makes both swift and cargo-specific passage through the NPC possible for large molecules. Their work appeared September 15 in eLife.

Scientists are paying close attention to this regulation since dysfunction in nuclear transport has been linked to many diseases, including cancers and developmental disorders.

While small molecules can easily pass in and out of the nucleus, the transport of large molecules such as proteins and RNA is more complex and less well understood. These are moved through the NPC rapidly, but also selectively to avoid allowing the wrong big molecules through.

It was already known that proteins called transport factors bind to large cargo and escort it through the NPC. A team led by Michael P. Rout, a professor at Rockefeller University and head of the Laboratory of Cellular and Structural Biology, and David Cowburn, a professor of biochemistry and of physiology & biophysics at Albert Einstein College of Medicine, sought to explain the speed with which transport factors ferry large molecules across the NPC, a process that lasts only a few milliseconds.

"It's understood how these transport factors selectively choose and bind to their cargo," Rout says. "However, it's been unclear how such a specific process can also shepherd molecules through the nuclear pore complex so quickly."

At the center of the NPC, the transport factors and their cargo must pass through a selectivity filter made of proteins called FG Nups. These proteins form a dense mesh that normally prevents large molecules from getting through. Using a technique known as nuclear magnetic resonance spectroscopy, the researchers collected atomic-scale information about the behavior of the FG Nups, focusing on Nsp1, the most studied representative of the FG Nups.

Normally, proteins fold into large structures. Relative to small molecules such as water, these large protein structures move very slowly. This means their interactions are correspondingly slow.

The researchers measured the physical state of FG repeats with and without transport factors bound to them. They found that rather than folding like proteins generally do, the FG Nups are loose and string-like, remaining highly dynamic and lacking a predictable structure.

"Usually, binding between traditionally folded proteins is a time consuming, cumbersome process, but because the FG Nups are unfolded, they are moving very quickly, very much like small molecules. This means their interaction is very quick," explains Rout.

The disordered structure of the FG regions is critical to the speed of transport, allowing for quick loading and unloading of cargo-carrying transport factors. At the same time, because transport factors have multiple binding sites for FG Nups, they are the only proteins that can specifically interact with them -- making transport both fast and specific.

"We observed that there is minimal creation of a static well-ordered structure in complexes of FG Nups and transport factors," says Cowburn. "Our observations are, we propose, the first case where the 'fuzzy' property of an interaction is a key part of its actual biological function."

The team hopes this discovery will lead to detailed characterizations of nuclear transport pathways and to more close studies of the NPC's function. Ultimately, a better understanding of how the NPC works will not only provide new insight into the basic biology of cells, but also have implications for health and disease.

Wynne Parry | EurekAlert!

Further reports about: Biology Rockefeller factors large molecules proteins small molecules

More articles from Life Sciences:

nachricht In focus: Peptides, the “little brothers and sisters” of proteins
12.11.2018 | Technische Universität Berlin

nachricht How to produce fluorescent nanoparticles for medical applications in a nuclear reactor
09.11.2018 | Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences (IOCB Prague)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

Im Focus: Nanorobots propel through the eye

Scientists developed specially coated nanometer-sized vehicles that can be actively moved through dense tissue like the vitreous of the eye. So far, the transport of nano-vehicles has only been demonstrated in model systems or biological fluids, but not in real tissue. The work was published in the journal Science Advances and constitutes one step further towards nanorobots becoming minimally-invasive tools for precisely delivering medicine to where it is needed.

Researchers of the “Micro, Nano and Molecular Systems” Lab at the Max Planck Institute for Intelligent Systems in Stuttgart, together with an international...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

In focus: Peptides, the “little brothers and sisters” of proteins

12.11.2018 | Life Sciences

Materials scientist creates fabric alternative to batteries for wearable devices

12.11.2018 | Materials Sciences

A two-atom quantum duet

12.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>