U.S. biochemist finds structural mechanism of cellular "gatekeeper"

A U.S. biochemist has determined the architecture and inner-workings of the inner ring of the nuclear pore complex (NPC), a key cellular "gatekeeper", the California Institute of Technology (Caltech) said on Thursday.

After a decade of research, Caltech biochemist Dr. Andre Hoelz successfully used X-ray crystallography and other techniques to make the finding, it said.

Many scientists thought it would be almost impossible to determine the atomic structure and mechanisms of a massive cellular machine that is vital for survival called the NPC.

The NPC serves as a cellular "gatekeeper", in charge of determining what proteins and other molecules are allowed to pass into the nucleus decisions that are crucial to cell survival, genetic mutations, and viral barriers.

The NPC is targeted by a number of diseases, including some aggressive forms of leukemia and nervous system disorders.

The NPC is composed of many copies of nearly three dozen different proteins, representing perhaps 10 million atoms in all, so solving its structure is a daunting challenge.

The central channel of the NPC was previously believed expandable, and could stretch open to permit large macromolecules to pass through then it could return to its normal size.

Released in a paper in the Aug. 27 issue of Science Express, Hoelz's conclusive new work shows that the inner ring is relatively rigid and the channel cannot dilate.

Discovering the structural mechanisms of the NPC could ultimately lead to new classes of cancer drugs. And because viruses frequently subvert the NPC to take over cells.

Figuring out how the NPC works also could lead to the development of powerful new drugs that block the action of those viral intruders, the university said. Endi