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

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 Nationa l 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.


'"/>

Source:University of Texas Health Science Center at Houston


Related biology news :

1. Beyond lithium for bipolar disorder
2. Beyond the book: Software automates access to brain atlases
3. Beyond the DNA: Chemical signatures reveal genetic switches in the genome
4. Its in the genes: Study opens door to new treatment of the blues
5. Lipids get new comprehensive classification system
6. Jumping gene helps explain immune systems abilities
7. Protein helps regulate the genes of embryonic stem cells
8. Scientists reveal the shape of a protein that helps retroviruses break into cells
9. Thai spice helps cut blood sugar swings
10. Chemists synthesize molecule that helps body battle cancers, malaria
11. Ancient DNA helps clarify the origins of two extinct New World horse species
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/9/2016)... -- Elevay is currently known as the ... high net worth professionals seeking travel for work   ... there is still no substitute for a face-to-face meeting. ... deal with a firm handshake. This is why wealthy ... citizenship via investment programs like those offered by the ...
(Date:4/26/2016)... , April 27, 2016 ... "Global Multi-modal Biometrics Market 2016-2020"  report to their ... , The analysts forecast the global ... of 15.49% during the period 2016-2020.  ... of sectors such as the healthcare, BFSI, transportation, ...
(Date:4/13/2016)... -- IMPOWER physicians supporting Medicaid patients in Central ... in telehealth thanks to a new partnership with higi. ... patients can routinely track key health measurements, such as ... when they opt in, share them with IMPOWER clinicians ... retail location at no cost. By leveraging this data, ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... ... June 23, 2016 , ... Supplyframe, the Industry Network for ... Design Lab . Located in Pasadena, Calif., the Design Lab’s mission is to ... are designed, built and brought to market. , The Design Lab is Supplyframe’s ...
(Date:6/23/2016)... NC (PRWEB) , ... June 23, 2016 , ... In ... University Hospital in Denmark detail how a patient who developed lymphedema after being treated ... tissue. The results could change the paradigm for dealing with this debilitating, frequent side ...
(Date:6/23/2016)... 23, 2016  Blueprint Bio, a company dedicated to ... medical community, has closed its Series A funding round, ... "We have received a commitment from Forentis ... need to meet our current goals," stated Matthew ... runway to complete validation on the current projects in ...
(Date:6/23/2016)... -- On Wednesday, June 22, 2016, the NASDAQ ... Dow Jones Industrial Average edged 0.27% lower to finish at ... Stock-Callers.com has initiated coverage on the following equities: Infinity Pharmaceuticals ... NKTR ), Aralez Pharmaceuticals Inc. (NASDAQ: ARLZ ... Learn more about these stocks by accessing their free trade ...
Breaking Biology Technology: