Dynamic Membrane Transporter Protein Designed From Scratch

Richard P. Feynman, the often-quoted physicist, once wrote: “What I cannot create, I do not understand.” Researchers putting that maxim into practice are now a step closer to understanding membrane-spanning ion-transporter proteins: They’ve created a simple version from scratch (Science 2014, DOI: 10.1126/science.1261172). Scientists have designed numerous proteins to bind metal ions or catalyze simple reactions in the name of understanding protein folding and function. Designing an ion transporter is more difficult because the design must account for multiple stable protein conformations that interconvert. William F. DeGrado took on the challenge with fellow University of California, San Francisco, researcher Michael Grabe, MIT’s Mei Hong, Dartmouth College’s Gevorg Grigoryan, and others. Their designed transporter, called Rocker, contains two interacting pairs of helices that rock between two forms—one open to the inside of a membrane, the other to the outside. Biophysical tests show the transporter shuttles zinc and cobalt ions, but not calcium ions, across a membrane. Rocker’s activity falls short of natural proteins. But that’s a minor point to Gaetano T. Montelione of Rutgers University, who comments that considering protein dynamics “is an important innovation, essential for creating a functional ion-transporting membrane protein.”