Putting It All Together
Science benefits from collaboration, and structural biology is no exception. This extends to our tools. To understand cells across their full length scale, we need to combine what we learn from different techniques. Consider this Bdellovibrio bacteriovorus cell. To visualize its overall structure, we can use cryo-ET. To identify a particular structure in the cell, we can alter its abundance (by genetically deleting it or overexpressing it) or use a fluorescent tag (⇩). Once we have identified a structure, we can get a higher-resolution view of it by sub-tomogram averaging. Then we can again use genetics to locate the positions of individual pieces in the structure (⇩). Combining this information with clues from other biochemistry methods, we can place high-resolution structures of components solved by X-ray crystallography and single particle reconstruction into their correct context. In this way, we can begin to build up a full picture, from individual atoms to entire cells. We still have a long way to go, but someday we hope to be able to map the location and interactions of every protein in a bacterium or archaeon, creating a true, molecular atlas of the cell.