Now, let's look at how those different amino acids are assembled to form complex proteins. Here is a few small amino acids. And here's an example of one large complex protein, hexokinase. Think of it again, as here are our LEGO building blocks, and here is the large Eiffel Tower that we have built out of LEGO building blocks. And, when we do this assembly, we can think of four levels of protein structure. First we'll start at the level of primary protein structure. You can just think of this as a list of amino acids lined up in a single chain that tells us how we glue one amino acid to another, to another, to form a long, nearly linear chain. When we look at the structure of the chain at the next level, we find that these chains tend to wind up to form either an alpha helix or a beta sheet where these folds and connections are stabilized by hydrogen bonds between different amino acids. Then at the tertiary level, there are attractions and interactions between different alpha-helixes and between alpha-helixes and beta-sheets that form more complex three-dimensional sheets, as these alpha helixes and pleated beta-sheets are glued together, if you like, with bonds. Say here, and here, and here, tying them together to make a tertiary protein structure. Finally, we'll go to the largest level, where we take, several of these amino acid chains, these tertiary structures. And assemble them together at the quaternary level. We glue together these sub-units to create complex proteins. And we'll go from single amino acids to proteins made up of thousands of amino acids. An example of a relatively simple and small amino acid is insulin, shown here. The chemical formula for insulin, is this complex list here. This just tells us that insulin is made up of 257 Carbons, 383 Hydrogens, 65 Nitrogens, 77 Oxygens and 6 Sulfurs. These are assembled into a number of different pro, amino acids. And each of these letters here correspond to a different amino acid on our list. If we go back to our list from the previous lecture, you can see each of the amino acids are labeled with a different letter. So for example, glutomine here is Q. And lycine is k,and we take those and assemble them together, to make the two different chains, and these amino acids bond together to make these alpha-helixes and beta-sheets. And they all glue together to make this more complex structure that we see here for insulin. The reason why we're so interested in the structure of proteins is for protein structures determine their function. And these proteins are the machinery that's responsible for life and basically drives life. When we look at our bodies, proteins make up more than half the mass of many cells, the rest is mostly water. And the rich list of proteins that make up our bodies enable it to carry out all the complex things it does. We know of over 10,000 different human proteins and our genetic information, our DNA is nothing more than instructions for how to put together different proteins. Now proteins do an enormous amount. They're responsible for structure. For enzymes, for hormones, for transportation, for protection against bacteria and viruses. They serve as sensors, toxins and gates. The way they do all these different things is each protein has a special shape that's designed to carry out a specific function. For example, let's consider this protein here. This protein's job is an enzyme whose role is to take this substrate, this green thing here, and separate it into two separate components. How does it do that? It has just the right shape to bond to this particular substrate. When it bonds to the substrate, the enzyme changes its shape slightly. As an enzyme changes its shape, it separates, the substrate into two pieces. And those two pieces are cleaved apart. And now return back to the cell. So this enzyme now returns back to its original shape. And having undergone this function, this enzyme, this protein serves as an enzyme and splits this substrate into these products. That's one role a protein can play. Another role a protein can play is providing structure, and this here, this triple helix is collagen. Collagen is the most common protein in mammals, and it provides the main component cartilage and bones and ligaments and tendons, skin. Here's a human bone and you can see the collagen provides the structure that it takes to hold our bodies together. And this is another role proteins play. Proteins can play the role of transportation. What proteins can do is they can move, say some material binds to some substrare, transports them to the cell. And then moves them through from the outside of the cell to the inside of the cell. And what's shown here is a very common class of transporters, called ABC transporters, that bind to ATP. And as we'll see, ATP is the fuel that enables our biology. Proteins serve as a way of protecting us against bacteria and viruses. There are proteins that have just the right shape that they can bind to a part of a bacteria and the shape matches with the bacteria shape. So that when it finds the right antigen it binds to it and destroys that, so it can protect our body against invaders. And our white blood cells, for example, are designed to produce the right proteins to protect us against invading bacteria. Proteins also serve as things like gates, so here is a particular protein that's controlled by the voltage in our cell. And as different voltages are applied, its shape changes so it can let some elements, say, calcium, flow in. And perhaps other gates will let things like sodium or potassium flow in or out. So by controlling these proteins with charge or by adding things like ligands, that interact with the protein, we can change the flow of material in and out of a cell. So proteins serve this enormous list of processes. And the tens of thousands of proteins in our body all carry out different tasks that enable our body to function. So now that we've gone from amino acids to proteins, we're going to go from nucleotides to DNA and RNA. And we're going to see a similar story where we build up complex structures out of simple elements. In the case of DNA and RNA, they're built up of nucleic acids, and nucleic acids all have the same general form. There's a base, a sugar, and a Phosphate. In the case of RNA, it's a d-ribose sugar. In the case of DNA, it's a deoxi-ribose sugar. And just like with proteins, we're going to take our basic LEGOs or basic building blocks, and tie them together to make complex chains. And these complex chains are going to do interesting things. Okay, so let's start with assembling DNA and RNA. And with DNA and RNA, all their rich structure and behavior is governed by five nucleotide bases. In the case of RNA, those bases are cytosine, uracil, adenine and guanine. C, U, A, and G. DNA reuses three of those bases and then replaces the U base with a T base. So they have very similar basic alphabets to make up the language of DNA and RNA. In the case of DNA, these bind together to make the famous double helix. And here's the double helix of DNA. And in the DNA double helix, the key structure of DNA is determined by simple rules that say the A base always binds to T, the T base always binds to A. C binds to G and G binds to C. So with these rules, that determines the structure of DNA. This simple set of rules let, enables DNA to replicate in a way that has a minimum number of errors in the replication process. So let's, what's shown here is a chain of DNA. C binds to G, T binds to A, and a given alphabet, as we'll soon see, will convey the set of rules for constructing proteins. Now what happens when we want to have, make copies of DNA? Well, what do we do? But, you have helicase come in and splice the DNA, split it into two distinct pieces. And then a polymerase comes along and reattaches bases to assemble copies of the DNA. And we follow this basic rule. Glue G to C, glue T to A, and in doing so, we end up making two identical copies of DNA out of the original DNA molecule. So we can, so one of the important roles DNA plays is it could replicate itself and make multiple copies as we copy cells. DNA also encodes instructions for making RNA. RNA is a single strand. So, like DNA, it's a strand-like molecule. It's the only single strand. And it's made up, again, of four nucleotides. What RNA does is it encodes instructions for making proteins. And you can read the RNA destruct, instructions. We can take RNA and each triplet of RNA is called a codon, codons made up of three nucleotides, and each codon is an instruction telling you which protein goes, attaches at which position. So what DNA does is it transcribes how to make this messenger RNA. And the RNA then describes how to assemble proteins. And this code, this list of codons are the instructions, the genetic code that tells you how to assemble proteins. So, how do we read this genetic code? Well we, as we saw, the genetic code is made up of three letters. And associated with the different three letter sets, are different proteins. Now, the code has a certain redundancy in it. So, some genetic code combinations encode, well, we have four combinations, all of which encode for the same protein. Other combinations encode for stops and starts. That tell you where, you know, that are the punctuations that tell you where the protein ends, and begins. And this genetic code you could think of as the operating system of life. You know, when you get your cell phone, your cell phone comes with many apps and you can download new apps on the web. When people write apps, they all use the same underlying language to write their computer code. You can think of life as operating the same way. This genetic code is the computer language, the operating system of life. If you would like to create a new protein, all you need to do is create DNA, or to encode RNA with the right set of letters, and it will tell you how to assemble that protein. The neat thing about this, is let's say, and so, we'll come back to this when we talk about evolution. That one bacteria figures out a new protein that it wants to encode. Maybe this protein protects it against, well, unfortunately a vaccine. This protein gives it immunity. It's genetic, since it uses the same genetic code as other bacteria to encode that message, it can share this useful innovation with other proteins. This ability to innovate and share innovations is a big advantage with a common operating system. We see this in the computer world, where a handful of operating systems tends to dominate. Things like personal computers or cell phones. Not because a given operating system is better than others, but because that operating system has many applications associated with it, and people buy the operating system for the applications. So, you can think about this operating system here, perhaps as the Windows operating system. May not be the best operating system available, but these set of rules became popular because everyone else was using them. Once you have these operating systems it gives you instructions for assembling protein. Now, protein assembly is a multistage process. We start with our DNA creating our messenger RNA. That messenger RNA tells us what the protein sequence is. We then have the transport RNA, the tRNA. And its role is to bind amino acids to the, here's our tRNA coming in. It, it contains a set of instructions on what to bind. The tR, tRNA brings in the right amino acid, it attaches to the ribosome, you can think of the ribosomes as kind of a work bench that gives you a place where you assemble the proteins together. So what we want to do is create this protein chain, our DNA has given us instructions on how to do that. That's encoded in our messenger RNA. The tRNA comes in, finds the right site to bind to, binds to the matching site, and we assemble the protein chain. So we've got this multi-step process. Where, the, ribosome and the RNA, in its two forms, assemble a protein. All of this take energy. And the energy source for this is going to be ATP. And this picture gives us our basic model of how proteins are synthesized in the cell. One of the key parts of this, is we need an energy source for all this assembly. And for our bodies, and for all of life, the energy source is ATP. And ATP is part of the cycle of metabolism. Metabolism is a process, is a biochemical process that exploits and uses energy, and what it does is we have two types of reactions. We have catabolic reactions that break down complex molecules. Say things like fatty acids that are a source of energy, and use that energy to convert ADP by adding a phosphorus to ATP. This has two phosphorus, this has three, so we add, we take some energy from our complex molecules, we assemble ATP, and that ATP is going to be our energy source for a lot of our biochemistry. We then run an anabolic reaction that takes ATP and converts it back to ADP. And this cycle is our energy cycle that powers our biochemistry. So let's go through our basic steps of protein synthesis. We start with our information archive, the DNA. And remember our information archive could be copied over and over to make multiple copies of the given cell. So DNA serves the role of both storage and replication. The DNA is the blueprint for making the RNA. The next step is transcription. We then use the RNA as the hardware for assembling the proteins in the presence of the ribosomes. So again, here's this flowdown, where we start with our DNA matched up in a double helix. That DNA transcribes the appropriate RNA. The genetic code translates each of these codons into a particular amino acid that's then assembled to make a protein. This seems to be the key ingredient for life on Earth, and there seems to be many elements we need for all this to work. We need a coding language, the genetic code, an energy source, ATP, a building tool or a workbench ribosomes, a blueprint DNA, a messenger system that takes the DNA and informs the ribosome how to make a particular protein, a transport system that brings in the amino acids, so that the ribosomes can assemble them into proteins, and a medium where all these rich processes happen. This is a relatively complex system. With many pieces, but a very versatile one that lets biochemistry assemble tens of thousands of proteins, out of a set of rules encoded by just four nucleotides on our blueprint DNA. Is this the only way life can function? We don't know, but this is the way life functions on Earth. And if we are going to speculate about life elsewhere, we need to begin by understanding life on one system. So let me end by giving you two assignments to go off and look up and assignments just to understand your own bodies better. Think about how many nucleotides there are in a human cell. And then go back, and to our earlier discussion and see how many amino acids there are in insulin. So why don't you look at those two and then we'll come back and see how we assemble, proteins and DNA to make up the cells that make up our bodies and all life on earth.
