Protein's path to the 'Chamber of Doom' identified

London, July 13 : In a breakthrough study, researchers have uncovered a deadly pathway of proteins in the cell, composed of a slippery tube that funnels proteins into a "chamber of doom" where they are shredded and recycled into the building blocks of new proteins.

This new pathway found by researchers from the Technion-Israel Institute of Technology and the University of Texas Health Science Center at San Antonio may have applications for Alzheimer's, Parkinson's and some cancers.

The researchers have described this tube as part of the 26S proteasome, an enzyme that acts as the cell's protein garbage disposal. They said that the tube is a concentric pile of rings surrounded by molecular motors that direct the proteins toward the proteasome's slicing and dicing core.

"The life of all proteins in our cells ends within the proteasome chamber of doom," Nature quoted Technion author Michael Glickman, as saying.

He also said that the newly-described pathway "should be of interest in applications for diseases in which cells are unable to process degraded or misfolded proteins," including Alzheimer's and Parkinson's disease, some cancers, and age-related conditions such as cataract disease.

The results may help the researchers to understand the basic biology of the proteasome and "its intrinsic essential function in a myriad of cellular pathways," said Allen Taylor.

Usually proteins that are marked for destruction with a ubiquitin protein "tag" are degraded by the 26S proteasome.

In fact, the proteasome itself is made up of two major structures: a large core structure where the proteins are degraded, and a smaller structure that serves as a kind of entryway where the tagged protein makes its first contact with the proteasome and is unfolded for its journey into the core.

And the tube described by the researchers is part of the smaller structure, and serves a chute between the first contact site and the core.

In the study, atomic force microscopy was used to visualize the extremely tiny tube, which were described as two molecular "donuts" stacked on top of each other. The donut holes through which proteins pass is only two nanometers in diameter.

The tube is surrounded by a group of energy-producing enzymes called ATPases, which act a motor to drive proteins through the tube.

"One may see the entire machine as an external engine wrapping around an inner molecular stent for protein translocation, all situated atop the molecular shredder into which the proteins are fed," explained Glickman.

He also noted that it's a natural design that engineers working on synthetic nanomachines might hope to copy in their own creations.

The study is published online in the journal Nature Structural and Molecular Biology.

ANI