Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Beyond genes: Lipid helps cell wall protein fold into proper shape

18.07.2005


It takes more than the genetically coded sequence for a membrane protein to fold and function. Its lipid environment also plays a role.



A protein that provides a vital passage through a bacterium’s outer cell wall will misfold and malfunction if that wall is built of the ’wrong’ material, scientists at The University of Texas Medical School at Houston report in a finding that has long-term implications for understanding diseases caused by misfolded proteins such as cystic fibrosis, Alzheimer’s disease, and mad cow disease.

The paper in today’s Journal of Biological Chemistry by Professor of Biochemistry and Molecular Biology William Dowhan, Ph.D., and colleagues shows that phospholipids, which make up the permeable barrier of cell membranes, play a direct role in the folding of membrane proteins – proteins that penetrate the membrane or bind to either side of it.


"What we’ve demonstrated again is that it’s not just a membrane protein’s genetically determined sequence that dictates how it folds so that it can function properly. Its lipid environment also plays a role," Dowhan said. "People used to assume that specific lipids made no difference."

In the JBC paper, Dowhan and colleagues looked at how a protein called GabP, which transports an amino acid across the membrane of the bacterium E. coli, is affected by the presence of a phospholipid named phosphatidylethanolamine, or PE for short.

Phospholipids, unlike their fatty acid and cholesterol cousins, include a phosphate group that spurs them to form a bilayer with water-friendly outer layers sandwiching an impermeable water-unfriendly inner layer that defines the outer surface of cells. Transport of nutrients and waste material across the cell membrane is then governed by the specific proteins associated with it.

In a strain of E. coli lacking PE, the GabP protein misfolded, with two areas of the protein inverting from their normal structure. The PE-lacking protein’s amino acid transfer rate plummeted to nearly zero, falling 99 percent compared to the transfer rate in unaltered E. coli with PE.

GabP is the third membrane protein that Dowhan and colleagues have shown to be affected by the presence of PE.

The team is using the E. coli model to discover how all proteins fold in the membrane, not just transport proteins such as GabP but also biosynthetic proteins that manufacture complex compounds such as proteins and fats out of simple compounds.

"The next goal now that we’ve defined the phenomenon is to get into the specifics, find the mechanisms by which these proteins fold. What part of the protein interacts with the lipid, and what part of the lipid with the protein?" said Dowhan, who holds the John S. Dunn Sr. Chair in Biochemistry and Molecular Biology and is on the Graduate School of Biomedical Sciences faculty.

Understanding the molecular basis for membrane protein folding will help researchers address serious diseases caused by misfolded proteins. "In cystic fibrosis, Alzheimer’s disease and mad cow disease, the dysfunctional proteins are associated with membranes," Dowhan said.

Membrane proteins make up 30 percent of known proteins. Dowhan estimates another 40 percent are loosely tied to membranes. "So you are looking at possibly 70 percent of biology occurring at or in a lipid membrane surface," Dowhan said.

Membranes and their surface proteins are accessible targets for pharmaceuticals, and most drugs target either membrane proteins on human cells or the membranes of pathogens.

Co-authors of the JBC paper with senior author Dowhan are first author Wei Zhang, Ph.D., a former graduate student who is now a post-doctoral fellow at Stanford University, and post-doctoral fellow Heidi Campbell, Ph.D., of the UT Medical School Department of Biochemistry, and Molecular Biology, and Steven King, Ph.D, associate professor, Department of Integrative Biosciences at Oregon Health & Science University.

Dowhan recently was granted a MERIT award by the National Institute of General Medical Sciences of the National Institutes of Health.

These rare awards provide long-term grant support for scientists whose research competence and productivity are distinctly superior and who are likely to continue to perform in an outstanding manner, the NIGMS notes.

MERIT (Method to Extend Research in Time) status essentially gives Dowhan a 10-year renewal to 2015 on his longstanding NIGMS grant "Structure and Function of Membrane Proteins" by providing back-to-back five-year grants of $2.4 million apiece.

In April, Dowhan received the prestigious American Society for Biochemistry and Molecular Biology Avanti Award in Lipids.

Scott Merville | EurekAlert!
Further information:
http://www.uth.tmc.edu

More articles from Life Sciences:

nachricht Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel

nachricht Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt

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 quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>