Biocurious is a weblog about biology, quantified.

Molecule of the Month: 70S Ribosomes

by PhilipJ on 6 January 2010

Ribosomes are one of the wonders of the cellular world, and one of the many wonders you can explore yourself at the RCSB PDB. In 2000, structural biologists Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath made the first structures of ribosomal subunits available in the PDB, and in 2009, they each received a Nobel Prize for this work. Structures are also available for many of the other players in protein synthesis, including transfer RNA and elongation factors. Building on these structures, there are now hundreds of structures of entire ribosomes in the PDB, revealing the atomic details of many important steps in protein synthesis.

After solving the structures of the individual small and large subunits, the next step in ribosome structure research was to determine the structure of the whole ribosome. This work is the culmination of decades of research, which started with blurry pictures of the ribosome from electron microscopy, continued with more detailed cryoelectron micrographic reconstructions, and now includes many atomic structures. By using small pieces of mRNA, various forms of shortened or chemically-modified tRNA, purified protein factors, and modified ribosomes, researchers have solved the structures of ribosomes in the act of building proteins. These structures are so large that they don’t fit into a single PDB file—for instance, the structure shown here was split into PDB entries 2wdk and 2wdl.

Looking at all the different forms of life on the Earth, we find that all living organisms have ribosomes and that they come in two basic sizes. Bacteria and archaebacteria have smaller ribosomes, termed 70S ribosomes, which are composed of a small 30S subunit and large 50S subunit. The “S” stands for svedbergs, a unit used to measure how fast molecules move in a centrifuge (note that the values for the individual subunits don’t add up to the value for the whole ribosome, since the rate of sedimentation is related in a complex way to the mass and shape of the molecule). The ribosomes in our cells, and in other animals, plants and fungi, are larger, termed 80S ribosomes, composed of a 40S small subunit and a 60S large subunit. Strangely, our mitochondria have small 70S ribosomes that are made separately from the larger ones in the cytoplasm. This observation has lead to the hypothesis that mitochondria (and chloroplasts in plant cells) are actually bacteria that were caught inside cells early in the evolution of eukaryotic cells. Now, they live and reproduce happily inside cells, focusing on energy production and relying on the surrounding cell for most of their other needs.

Read more from David Goodsell at the RCSB PDB, here.

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Molecule of the Month: Designed DNA crystals

by PhilipJ on 6 November 2009

DNA crystal

DNA is a perfect raw material for constructing nanoscale structures. Since base-pairing has been selected by evolution to be highly specific, it is easy to design sequences that will link up with their proper mates. In this way, we can treat small pieces of DNA like Tinkertoys, designing individual components and then allowing them to assemble when we put them together. In addition, the chemistry of DNA synthesis has been completely automated, so custom pieces of DNA can be easily constructed, or even ordered from commercial biotech companies. This puts DNA nanotechnology in the hands of any modest laboratory, and many laboratories have taken advantage of this, creating nanoscale scaffolds, tweezers, polyhedra, computers, and even tiny illustrations composed entirely of DNA.

DNA has the characteristic mix of flexibility and rigidity that is the hallmark of biological molecules. If the sequence of bases is correct, it zips up into a double helix that, at least in short lengths, is a sturdy cylinder. Longer stretches, however, start to show flexibility, and the DNA helix curves and bends. The trick in designing a DNA infrastructure is to develop ways to rigidify the overall structure. In most cases, this has been done by having the DNA strand weave back and forth between many parallel double helices. In this way, the bundle of helices form a structure that is far more rigid than a single helix.

Nadrian Seeman pioneered the use of DNA for building nanoscale structures. After decades of work, the structure shown here, from PDB entry 3gbi, is the first crystal structure of a DNA lattice completely designed from scratch. It is built of small 3D triangular subunits, each composed of three separate types of DNA strands. The base sequences are carefully chosen so that they assemble into this one particular structure, and not any others. At the corners of the 3D triangle, there are sticky ends that link to other triangles, stacking up in a predicable way into a three-dimensional scaffold.

Read the rest from David Goodsell at the RCSB PDB here. We’ve covered some of this kind of work before, too.

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Molecule of the Month: Na-K Pump

by PhilipJ on 20 October 2009

Na-K Pump

Our bodies use a lot of energy. ATP (adenosine triphosphate) is one of the major currencies of energy in our cells; it is continually used and rebuilt throughout the day. Amazingly, if you add up the amount of ATP that is built each day, it would roughly equal the weight of your entire body. This ATP is spent in many ways: to power muscles, to make sure that enzymes perform the proper reactions, to heat your body. The lion’s share, however, goes to the protein pictured here: roughly a third of the ATP made by our cells is spent to power the sodium-potassium pump.

The sodium-potassium pump (PDB entries 2zxe and 3b8e) is found in our cellular membranes, where it is in charge of generating a gradient of ions. It continually pumps sodium ions out of the cell and potassium ions into the cell, powered by ATP. For each ATP that is broken down, it moves 3 sodium ions out and 2 potassium ions in. As the cell is depleted of sodium, this creates an electrical gradient and a concentration gradient, both of which are put to use for many tasks.

The most spectacular use of this gradient is in the transmission of nerve signals. Our nerve axons deplete themselves of sodium ions, then use special voltage-gated sodium channels to allow the ions to rush back in during a nerve impulse. The sodium-potassium pump has the job of keeping the axon ready for the next signal. The gradient also helps control the osmotic pressure inside cells, and powers a variety of other pumps that link the flow of sodium ions with the transport of other molecules, such as calcium ions or glucose.

Read the rest by David Goodsell at the RCSB PDB, here.

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