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
Source:University of Texas Health Science Center at Houston