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Matching up positive and negative charges on two of its subunits may allow the TatA membrane transporter to penetrate the lipid bilayer.
June 1, 2013|
COURTESY OF STEPHAN GRAGE AND ANNE S. ULRICH
T.H. Walther et al., “Folding and self-assembly of the TatA translocation pore based on a charge zipper mechanism,” Cell, 152:316-26, 2013.
TatA proteins are believed to come together to form large pores in bacterial membranes to transport folded proteins. But two of the protein’s segments are covered in positive and negative charges, which would make it difficult for them to penetrate the lipid bilayer—a process believed to be necessary for protein transport. Now, Anne Ulrich of the Karlsruhe Institute of Technology in Germany and colleagues report that corresponding charges on the two cytoplasmic segments of TatA align, effectively neutralizing each other, and allowing the formation of a membrane-crossing pore.
The peculiar pattern
The researchers noticed that the pattern of charged amino acids along the helical section of the TatA subunit, called an amphiphilic helix (APH), aligned with opposite charges found on the third subunit, the C-terminal densely charged region (DCR). “We realized that this was a very unusual symmetry—that charges were complementary over a long stretch in the linear protein sequence,” Ulrich says.
Using computer simulations, Ulrich and her colleagues also found that the two segments—APH and DCR—folded into a position that allowed the formation of salt bridges that effectively neutralized the charges. The researchers confirmed these findings in vitro by introducing mutations in one segment, which changed some positive charges to negative and some negative to positive, disrupting the bridges.
How exactly the zippered proteins fold into the membrane remains unclear, however, says Jan Maarten van Dijl of the University Medical Center Groningen in The Netherlands. “The authors look very nicely at assembly of TatA subunits and they do molecular dynamics, but they don’t measure [membrane transport] activity.”