X-ray crystallography has revealed the atomic make-up of several stable and plentiful complexes, such as the ribosome, the photosynthetic and respiratory chain complexes, and the proteasome7.
For example, the ribosome3,4 is organized into two subunits that join to read mRNA and then split after the protein is made. The barrel-like proteasome consists of four stacked rings around a central core lined with protein-degrading enzymes. ATP synthase is like a rotary motor powered by the proton flow along the membrane (Fig. 3; ref 8).
A detailed understanding of the structure of these machines is prerequisite to elucidating their function; however, the large size, fragility and scarcity of certain complexes means that high-resolution structural information can be hard to come by. This is made more challenging by the fact that many macromolecular complexes change shape as they perform.
Understanding the structure and function of these intricate machines is central to comprehending the cell, as well as certain disease processes. For example, mitochondrial dysfunction associated with certain neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, might reflect a breakdown of membrane organization.
It is increasingly clear that macromolecular complexes operate in a controlled, coordinated fashion within the highly ordered environment of the cell. Each macromolecular complex occupies a particular position, with the location and copy number influencing function. It was recently shown, for example, that mitochondrial ATP synthase is not distributed haphazardly through the membrane, but is arranged in long rows of complex dimers that influence the local membrane curvature9.
>> Macromolecular complexes operate in a controlled, coordinated fashion within the highly ordered environment of the cell. Each macromolecular complex occupies a particular position, with the location and copy number influencing function.
Investigating these interactions and processes is a promising but relatively unexplored field that offers opportunities in most areas of chemical, physical, engineering and life sciences. Estimates of the number and location of these macromolecular complexes are now coming into focus.
Many questions and practical challenges remain. Obtaining sufficient quantities of pure, functional macromolecular complexes for biochemical and structural analysis is difficult. The exact molecular components of many of the larger complexes remain a mystery, as do their distribution, dynamic nature and ability to self-assemble. Moreover, it is unclear how these machines interact and operate within the larger context of the cell.