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Scientists reveal details of calcium 'safety-valve' in cells
Date:6/6/2014

ovarian, and lung.

"Our work using the prokaryotic version of this protein has enabled us to construct a three-dimensional model that can be used as a basis for the rational design of possible inhibitor molecules," said Qun Liu, a scientist at NSLS and NYCOMPS and the lead author on the paper.

The atomic-level structures were determined using x-ray crystallography at NSLS beamlines X4A and X4C. Interactions of x-rays with the 3-D lattices of the protein molecules produce diffraction patterns from which the 3-D molecular images were derived. The images reveal a novel structure consisting of a centralized helix wrapped by two novel triple-helix sandwiches that traverse the membrane. The central portion can take on an open or closed conformation dependent on the acidity level, or pH. At physiological pH, open and closed conformations exist in equilibrium, maintaining a steady of state of calcium in the cell by allowing gradual leakage of calcium across the membrane through a transient transmembrane pore.

"This leak is intrinsic to all kinds of cells and is cytoprotective for life, similar to a pressure safety value used in a standard steam boiler for safety assurance," said Liu.

The studies reveal in detail how the TMBIM protein senses and responds to changes in acidity to precisely regulate the mechanism.

"The next step will be to solve crystal structures of the human TMBIM proteins to refine the design of possible inhibitor drugs," said Liu.

That work will take place at a new light source nearing completion at Brookhaven known as NSLS-II. That facility, set to start early experiments later this year, will be 10,000 times brighter than NSLS, making it particularly suitable for studies of membrane proteins, which are difficult to crystallize.

The New York Structural Biology Center is working in partnership with Photon Sciences at Brookhaven to build a microdiffraction beamline, called NYX, for advanc
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Contact: Karen McNulty Walsh
kmcnulty@bnl.gov
631-344-8350
DOE/Brookhaven National Laboratory
Source:Eurekalert  

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