Introduction
Protein machines are the key players within each living cell. Any major process required to maintain a cell, tissue or organism depends on the constant running of protein machines every day and all day. The size of these machines can range from a single molecule, often involved in control processes of more complex pathways to large, multi-component assemblies created by combining a variety of different protein and non-protein entities like DNA/RNA and small chemicals.
In many ways, these tiny machines inside each cell operate in the same way as a mechanical machine. Where a man-made machine like a car will need petrol or diesel, a protein machine will also require some form of energy, often as adenosine triphosphate (ATP) or some other phosphate molecule, to drive it. Different protein components will assemble and operate like axles, gears and conveyor belts and their architecture, construction and assembly is highly specialised for the chemical processes they carry out.
As with any manufacturing process in our human world, cellular processes carried out by protein machines are tightly controlled. Where a computer software may be used to send control signals to a machine in a factory, cellular signalling is relayed by small molecules shuttling around a cell. They activate or deactivate individual protein machine components and regulate their performance through chemical modifications such as phosphorylation and dephosphorylation.
Protein machine health is also monitored and if an assembly shows signs of damage or age it is labelled for recycling and removed from a process. Either the entire machine or selected components are broken up into their amino acid building blocks for reuse in protein production. As with any well-managed and organised manufacturing process in the human world, protein machines are optimised to be highly efficient in keeping waste, in particular energy, to a minimum.
Examples of protein machines
FoF1 ATP synthase
FoF1 ATP synthases (Figure 1 A)) represent the core protein machinery in the production of ATP. They are composed of two subcomplexes Fo and F1, named after their ability or lack thereof to bind oligomycin (“o�). Fo is located within the cell membrane of prokaryotes whereas in eukaryotes it is found in the thylakoid membrane of chloroplasts or the inner membrane of mitochondria. The catalytic F1 subcomplex, which catalyses the reaction of ADP and inorganic phosphate to water and ATP always faces towards the “inside�, i.e. the cytosol in prokaryotes, the stroma in chloroplasts and the matrix in mitochondria, to avoid loss of ATP, a cell’s energy currency and basic fuel for all other processes, to the “outside�. A proton gradient across the membrane is used to drive the machine. Here, the protons move from a high concentration to a low concentration. This is like water driving a waterwheel to make the shaft in a mill go round to drive the mill stones. As with mechanical gears, the FoF1 ATP synthase can also work in reverse, under the expense of energy, and decompose ATP into ADP and inorganic phosphate and actively move protons to the “outside�. How many protons need to be moved across the membrane, is different for each species and is defined by the number of components in the membrane-inserted ring of c proteins, i.e. the number of teeth on a gear within the Fo subcomplex.
Ribosome
Ribosomes (Figure 1 B)) are essential molecular machines responsible for protein synthesis in all living cells. They translate messenger RNA (mRNA) sequences into amino acid chains, forming functional proteins. They function like a conveyor belt reading the mRNA while it passes through the machinery and growing a peptide chain which folds into a functional three-dimensional protein structure. All ribosomes are constructed similarly, a small and large component, but differ in the specifics depending on where in the cell they are located and what type of protein they are synthesising. Its small component (30S in prokaryotes and 40S in eukaryotes) mainly carries the translation function of the machine and is associated with the mRNA. The large component (50S in prokaryotes and 60S in eukaryotes) contributes most to the catalytic function of protein synthesis and interacts with transfer RNA that shuttles individual amino acids to the active site for peptide bond generation. Ribosomes can be found either freely floating in the cytoplasm or attached to the endoplasmic reticulum in eukaryotic cells. They can combine into polysomes and translate the same mRNA multiple times in parallel. Their function is crucial for cellular growth, repair, and overall metabolism.
Kinesin, dynein and microtubules
Involved in cargo transport around a cell are motor proteins like kinesin and dynein (Figure 1C)). They use ATP as fuel to make their way along intra-cellular motorways, microtubules (Figure 1D)), that run through the entire cell in any direction and also serve as scaffolding and support to strengthen a cell.
Actin and myosin
Actin and myosin are key components in muscle cells and muscle contraction. Smooth muscles, like those involved in the digestive system, need to contract to mix the food in the stomach and push it through the intestines. Skeletal muscles are needed for locomotion and cardiac muscles are only found in the heart. Skeletal and cardiac muscles exhibit a stripy pattern due to the highly structured protein organisation in their respective cells. Actin and myosin interact with each other to facilitate muscle contraction at the expense of ATP. The sliding filament theory is used to describe this contraction. Here, myosin heads bind to actin filaments and in a stepwise manner shorten the distance between the two ends within a sarcomere, a muscle cell’s basic building block. Multiple sarcomeres are combined in a single cell which then form together a muscle. Through this combination the small single shortening within a sarcomere is amplified into a large muscle contraction.
Featured structure: Death-associated protein kinase 3 (DAPK-3; a.k.a. Zipper-interacting protein kinase ZIPK)
DAPK-3 (PDB: 3BHY) is one of five DAPK proteins, which belong to the family of calcium/calmodulin-dependent kinases. DAPK-3 is involved in the regulation of apoptosis (programmed cell death), autophagy, transcription, translation and actin cytoskeleton reorganization. It functions as a serine/threonine kinase by phosphorylating its target molecules. Some of its targets are components of myosin and ribosomes.
Melanie Vollmar
About the artwork
Freddie Gould (year 9) chose the protein Zip Kinase because it reminded him of a machine. He chose dark, grungy colours linking his art to a previous project about Steam Punk. The colours also reflect how it would look like in a machine body.
View the artwork in the .
Structures mentioned in this article
Further reading
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