Proteins in Action

So why are we going into all this tedious detail about how proteins function?

Because I want to explain how the genes control the information of the individual organisms and of the whole ecosystem. Maybe you only need to know that a gene can “turn on” and “turn them off,” and that’s how they control when and where the functions happen. Pigmentation happens only in pigment cells by producing the enzyme that causes pigment to form. Only in pigment cells. Or that most hormones influence cells, even though the hormone is outside the cell, because the cell has a protein on its cell surface that can respond to the hormone. Or that you can’t have the structures of your muscles (or their functions) unless the genes turn on (in muscle cells) that make the necessary proteins. Also none of these things can happen without organic energy that is available in the form of ATP that we have already discussed.

Protein functions depend upon their shapes. Every different kind of protein has a different shape.

Imagine here that the gray shape is a protein. Remember that “shape” means the physical distribution of the atoms and also the distribution of the energy. Physically the shape of the interacting molecules must fit together. In addition, energy interactions depend on the energy charges that are distributed over the surface of the molecule (or not). Positive charges attract negative charges. Similar charges repel each other. If there is no charge, the molecule usually is not inclined to interact.

Now imagine that the gray protein, on one of its sides, has an area that exactly attracts the black molecule. So whenever a black molecule is in the neighborhood it will pop right into the gray protein and stay there as long as conditions permit. And because the two molecules are attracted to each other, the energy relationships settle into a slightly new organization. As the energy relations over the protein readjust slightly to cuddle up to the black molecule, this causes all of the gray molecule to slightly shift. The shift moves charges and shapes all over the molecule until in this example the other side of the molecule is molded into a perfect “shape” to attract a third molecule. In the presence of ATP to provide the energy, these changes cause an important function to happen in the cell. And that function causes the gray protein to spit out both other molecules and return to normal. So it can do the same thing over again.

Or a receptor protein may be floating in the lipids of the membrane that surrounds the cell. The cell is maybe in an ovary and a hormone floats by. If the receptor is just the right shape to grab hold of the hormone, then the receptor-hormone complex will form and the receptor protein will be changed just enough that it activates something inside the cell.

In this way, and in other ways, the “shapes” of proteins are specific to their functions, and because they are specific they can be used to carry information from the gene to perform some action. Or proteins may be part of the structure of the cell. But to say again (and somewhat oversimplify), the point is that nothing happens unless the gene turns on to produce the protein and organic energy is available to activate the function of the protein.

The flow of information through the cell, the organism and the ecosystem is coded in the genes — the flow of energy discussed in chapter one is required for any work — the two paths cross to regulate almost everything that happens in life.

Protein Structure

A protein is a molecule that consists of amino acids joined together by covalent bonds. The code for this sequence of amino acids is preserved in a gene.

Last time we said the second thing we need to know about proteins is that each different kind of protein has a specific three-dimensional “shape” that is well designed to direct it’s own specific job for maintaining the life of that cell. The shape of the protein is perfect for whatever job it is supposed to do and is also perfect to interact with the source of energy that is needed to do that job.
The idea of “shape,” I am embarrassed to tell you this, is something of a metaphor for a set of characteristics that make up a protein in it’s final configuration, and also make it capable of adjusting to the conditions around it so that it can do its function(s) in an automatic response to those conditions.

Of course, we can’t really see what a protein is doing, so we require models that are based on the unchanging natural laws of chemistry and physics and the behaviors of the proteins, as they can be measured in various kinds of environments. I will try to describe a model for protein shapes.

Proteins are made of amino acids. Proteins are usually big molecules. Amino acids are rather small molecules. Molecules are atoms joined together with energy bonds, or they are bigger molecules made by joining together smaller molecules.

We should remember that atoms and molecules cannot be joined in just any old combination, but that every kind of atom is different in its distribution of energy. Some kinds of atoms join with others more strongly or less strongly or not at all. The distribution of energy in an atom, if the atom is part of a molecule, influences the distribution of energy in the molecule. And that is influenced by the energy of the environment. The environmental energy is usually measured as pH (that is, whether the environment more acid or more basic).

So. It is complicated.

We do not need to discuss all those complications. We only need to know they exist and understand that the “shape” of a molecule depends on the energy interactions among the atoms in the molecule and also the pH of the environment. We also need to know that the energy reactions are of two major sorts:

1. Covalent energy bonds are very strong and do not change without the help of an enzyme;
2. Weak energy bonds are constantly readjusting themselves depending on local conditions.

The primary structure of proteins consists mostly of the covalent bonds that attach one amino acid to the next amino acid in a long (or sometimes shorter) string of amino acids. These are the essential amino acids that we must eat in our diets in order to be healthy.

AminoAcid → AminoAcid → AminoAcid → AminoAcid → AminoAcid
(those arrows are strong covalent bonds)

The genetic code determines which amino acid will be where in this string and how long the string will be. Every different kind of protein has its own unique sequence of the specific kinds of amino acids, because it is made by its own specific gene.  The gene carries the code for the primary structure of the protein. We will discuss this later, but we have already said the function of many or most genes is to preserve this code and also to make sure the proteins are produced at the right time and place in the cell.

Once the sequence of the protein is firmly fastened together by covalent (strong) energy bonds that join the amino acids end to end, then there may or may not be one or a few covalent bonds created that join the sides of one or a few amino acids.  If these are present, they bend the protein molecule into its secondary structure.

The protein is then released into the cell where it folds up into a tertiary structure or shape. The tertiary structure of a protein.  The covalent bonds are formed by enzymes, but the tertiary structure is automatic as the protein folds up in response weak energy bonds that form among the various amino acids.

The weak bond is shown between the sides of two amino acids by the gray arrow; the strong bonds between their ends as black arrows. There are several different kinds of weak bonds.  Some weak bonds are stronger than others, all of them can be influenced by the pH of the environment.  The ends of every amino acid are the same.  This is why every amino acid as able to make a strong covalent bond with every other amino acid.  The sides of every kind of amino acid are different.  The proteins fold up, after the strong bonds are formed, because the sides of some of the amino acids will attract each other, some will repel each other and they will all finally settle into the configuration that is most comfortable for them all together.

Sometimes proteins pair up with other proteins by weak bonding or strong bonding.  Hemoglobin is an example. It consists of four molecules of protein — two of one kind and two of another kind.  These function together to carry red blood cells in the blood. If a protein consists of more than one chain of amino acids (polypeptide chain), its final structure is referred to as  its quaternary structure.

So, that is why proteins come in different shapes. The thing to remember from all this information is that each protein has the right shape to do one specific function in the cell. The covalent bonds make sure the primary structure is strong, and the weak bonds of the protein can adjust themselves to make the shape change just slightly when the conditions change.

The Most Important Thing About Proteins

This is where the rubber meets the road — Oops, that’s another metaphor. Where the flow of energy that we spent all of chapter one talking about, meets the flow of information. Anything that important just has to be complicated, and indeed it is mind-boggling if we think only of the individual processes. But it’s incredibly beautiful if we look at the big picture.

The first most important thing we need to know about proteins is they are made inside the cells at the right time in the right place because of the genetic code. We introduce this idea in the past few weeks and will return to it soon.

The second most important thing we need to know about proteins is that each different kind of protein has a specific three-dimensional “shape” that is well designed to direct it’s own specific job for maintaining the life of that cell. Every kind of protein has it’s own perfect shape that is preserved in its own gene. The shape of the protein is perfect for whatever job it is supposed to do and is also perfect to interact with the source of energy that is needed to do that job.

The third most important thing we need to know about proteins is that they function at the intersection of information and energy in the cell, and also in the ecosystem.

Today we will talk about the relationship between the shape of the protein, the specific job the protein is designed to do, and the energy source that is necessary to do any work in the cell. We will concentrate on the latter two and talk more about conformation (shape) next Thursday.

Some important proteins are the same in all cells (nearly all). Some, like your muscles, are in specialized cells. Some proteins, when they are mature and fully structured, attach to other proteins of the same kind, some to proteins of a different kind. All proteins and most other molecules get the energy from cellular respiration to do whatever specific work they do. The energy is released in mitochondria. It is circulated by ATP. We need an example to visualize these processes, so we will use muscles. If you want to know specifically how muscles work, that information is on the web. We are talking about the relationship between work and energy and the specificity of the proteins.

Muscles are composed of more than two kinds of proteins attach together, but the two major ones are actin protein and myosin protein. Of course the proteins are microscopic, but they organize together in large bundles, and the final result is a muscle. Move your hand to your face. The muscles on the inside of your arm become shorter (contract) because actin and myosin interact with each other. They actually move across each other so the two ends of the muscle come closer together (contract). Of course, it is work to contract a muscle. If you stop doing the work of holding the muscle short, then your arm can fall loose again. If you need to pull your arm up behind you, then a different set of muscles on the back side of your arm will contract. Muscles don’t do work to expand. They can use energy to contract or they can stop using energy and let the muscle get longer again.

It works like this. My brain is attached to my various nerves and the various nerves are attached to many things, but this particular nerve we are talking about is attached to a muscle in my arm. Big long nerve, runs all the way down my arm. When I put my hand on the hot stove, nerves in my hand send signals up to my brain (or maybe only as far as my spinal nerve). My brain thinks “ouch” and at the same time (actually faster than the ouch) it sends a signal down a different nerve to my arm that contracts the arm muscles that remove my hand from the stove. Every step of this process requires specialized proteins (and other sorts of molecules) and also requires energy that we discussed in chapter one. (The PDF of chapter one is available on the right of this blog.)

What do the proteins have to do with this? There are hundreds of different kinds of proteins. Each kind has a different conformation (shape) that makes it suitable to do a specific function, but nearly all of the actions require energy. Energy is the ability to do work. The energy comes from cellular respiration, and the energy gets into the molecules in the first place by the process of photosynthesis that happens in plants. Cellular respiration occurs in mitochondria. It is the process that breaks down a larger organic molecule, glucose, so that energy is released, and then it captures the energy. The energy is moved from the mitochondria to the location where energy is needed by a molecule named ATP. The ATP contains the energy as an energy bond.

The energy bond is carried around in the cell by a phosphate group. A phosphate group is so important it has a shorthand designation Ⓟ. It is a very tiny little group of atoms that can be carried around inside the cell as part of a larger (but still small) molecule that is called ATP (adenosine triphosphate). Adenosine plus three phosphate groups fastened end to end, or A~Ⓟ~Ⓟ~Ⓟ. The trick is that the third phosphate group on this tri-phosphate molecule can be transferred to any other molecule that needs the energy. For example a muscle molecule. When the third phosphate group is transferred to the muscle molecule, along with the energy bond that attaches it, the muscle molecule changes its shape in the tiniest but most important fashion that causes the muscle to contract. How exactly?

How exactly is not the most important part of this story. There are two most important parts to the story.

First, every protein molecule is a different and very specific shape, and that shape is just perfect for it to do its job(s). One part of the muscle job is to be able to attach to a phosphate group. When it attaches to the muscle, the phosphate group changes the “shape” (it changes the relationships among many of the energy bonds) of the muscle molecules so the actin moves a teeninsy bit across the myosin and the muscle is that little bit shorter. That little job of work changes the “shape” of the proteins back again to what they were, as the work absorbs the added energy, so the phosphate group falls off and floats away in the cell. Then the muscles will repeat this process millions of time to do their work. This is happening all over the muscle when it needs to contract. Lots of ATP molecules bring lots of phosphate groups to the muscle.

So to summarize, A~Ⓟ~Ⓟ~Ⓟ actually transfers the third phosphate group ~Ⓟ to the muscle, so it uses its energy to bond with the muscle proteins. We might think of this as muscle~Ⓟ. This changes the energy relationships inside the muscle proteins so their “shape” changes. As the work is done, the energy is lost, and the Ⓟ falls off the muscle. The tiniest bit of work has been done and the energy and the phosphate group are gone away, a bit of energy is changed to heat, and the muscle returns to its resting “shape.” (That’s why your muscles get warm when you are doing work.)

Now the muscle cannot do any more work until it gets more energy. The ATP has become ADP (A~Ⓟ~Ⓟ) that is adenosine di-phosphate (tri means three, di means two). It is no longer a high-energy a molecule. It returns to the mitochondrion.

The mitochondrion is an organelle (an organelle is an intracellular structure that contains many molecules that work together to perfom some particular function of the cell) inside of eukaryotic cells that has the function to break apart high-energy organic molecules and capture some of the energy that is released. That captured energy is used to re-attach phosphate groups to ADP molecules so they become ATP again and can then go back to the muscle and give it more energy so it can do more work. As we have seen before (chapter two), the molecules (physical things) cycle and cycle over again, while the energy does not. The energy is changed from a high-energy form to a low energy form and then is lost from the system as heat. This is the basic story of all life on earth at all the levels of organization.

In chapter one (available as a download on the right side of this blog) we explained WHY energy is required to maintain any kind of life including our whole living earth ecosystem. We have just now described HOW it happens. But let us summarize, because we should never forget that all of the energy for life on this earth comes from plants.

1. The plants use energy from the sun to make the high-energy bonds of organic molecules. This is the process of photosynthesis.

2. We eat the plants, or we eat some animal that ate the plants, because the only energy we can use to stay alive is organic energy, that is, the energy bonds that do the work of bonding together the atoms of organic molecules.

3. After we eat the high-energy organic molecules (carbohydrates, proteins, lipids and nucleic acids), they are broken down in a long trail of events that make the molecules for our for our bodies from the raw materials we eat. Energy is also released and is manipulated in the mitochondria, where larger carbohydrate molecules are broken apart to release smaller, low-energy molecules, water and carbon dioxide.

4. Much of the energy is captured and used to attach phosphate groups to ADP molecules, thus energizing them to become ATP.

5. The small ATP molecules are able to float around in the cell and interact with all the molecules that require energy to do work. Most of these are proteins.

6. This is done by transferring the phosphate and its energy to the protein (or wherever it’s needed). The protein then absorbs the energy, causing work to happen by changing the energy relationships (“shape”) inside the protein. The energy is gone from the phosphate into the protein, so the phosphate is no longer bonded to the protein and it falls off.

6. The result is work plus ADP plus an unattached phosphate group.

7. The ADP and the Ⓟ return to the mitochondria. The energy that was used to do the work is converted to a lower form, heat energy, that can’t be used in biochemical processes and so radiates out of the system.

So, we are at the intersection between the flow of energy, and the flow of information through the ecological system. Energy flows through space, from a higher form to a form that can be used by life, to a lower form that goes away never to return. Information also does not recycle, but it flows along through time, within the system. Only the materials recycle.

So now we have again described the flow of energy through the living system and away. This time in a cell. But we have added the idea that the proteins, by being specific for particular jobs, direct the way in which the energy is used in the cell. We used an example of muscle proteins, but every protein has its own specific function. And each kind of protein does its functions because of the genetic code that determines how how each will be “shaped,” and also determines when and where each will be produced in the cells.

Next Thursday we will talk about how the proteins are “shaped.”

Nucleic Acids and Proteins

Nucleic acids and proteins are organic molecules in living cells that carry the code of life from one generation to another, and also respond to conditions in the environment by modulating the behavior of cells, organisms and so the ecosystem.

Nucleic acids are long, very long molecules that are made in the nucleus of every cell (don’t bother me with the exceptions) by an elegant process that uses strong energy bonds and enzymes to join together the small nucleotide molecules of which they are composed. Some people study the nitty gritty of these processes and it is not difficult to find information about the details. For us, it is important to know that the strong energy bonds are strong and therefore do not come apart (unless some specific enzyme breaks them apart) and that the nucleotides can join to each other in any sequence.

There are two major types of nucleic acids. DNA maintains the code of life and passes it along (in chromosomes) to the next generation every time a new cell is made. The subunits of the chromosomes are genes. Each gene carries the code the cell uses to make one special kind of protein. RNA uses the code of each gene to make its specific kind of protein. Every different kind of protein has a specific job (biological function) to do in the cell or in the body. Altogether, that is how the body knows to do all of its functions, from making muscle cells to making pigment cells to responding to outside conditions. (And you thought you did all that.)

The DNA code consists of four different kinds of smallish nucleotide molecules. The four different molecules can be bonded together in any sequence, and it is the sequence that makes the code. It is important to remember this is not a random process. (Or it would not be possible to pass the code from one generation to the next, right?) We need to remember that the strong bonds between nucleotides do not normally come apart. We do not need to know exactly how enzymes control this process. The four nucleotides of DNA are named adenine, thymine, cytosine and guanine. I do not know why, and it is more convenient and is traditional to refer to them as A, T, C and G. If a particular genetic code of one of your genes is ATCGCCATTGGCA (in a sequence of thousands in one gene or millions in one chromosome), that means every cell in your body contains a gene with the sequence adenine, thymine, cytosine, guanine, cytosine, cytosine — and so on as part of a gene that is part of a chromosome. That chromosome you received from your father or your mother and you may pass along to your children. DNA is the code of life that is passed from generation to generation.

RNA uses the code of life to make specific proteins. Because it has a different function, the RNA molecules use a slightly different combination of molecules to copy the code. Instead of thymine, RNA uses a nucleotide called uracil. So the same code might be AUCGCCAUU (and so on). We do not need to know the specific code for any protein — only that every different kind of protein has a different code and a different function in the body.

We do need to know that each nucleotide is fastened to the next nucleotide in the series by a strong energy bond.

We also need to know that every different molecule also interacts with other molecules by weak bonds. Every molecule is made of atoms, of course, and every different kind of molecule is made of a different combination of atoms joined together with energy bonds. The weak bonds or weak repulsions happen because the positive and negative energy of the bonds usually is not completely uniform, all over the molecule. Water molecules, for example, are made of one oxygen atom and two hydrogen atoms that are joined together with fairly strong energy bonds that stay bonded most of the time. However, they also have a tiny bit more of a positive charge on one side and a tiny bit more of a negative charge on the other side. Because of these tiny charges, water molecules are attracted (but not strongly bonded) to each other and to other molecules that also have tiny charges on different parts of themselves.

Molecule = A group of atoms joined together with energy bonds.

Chromosome = a subcellular structure (we can think of a chromosome as an organelle) composed of DNA (and some other molecules) that carries the code of life from one generation of cells to the next.

Organelle = a structure inside a eukaryotic cell that is made of different kinds of molecules that are organized together to do a particular function inside the cell. (Prokaryotic cells are mostly bacteria. They do the same functions but they lack organelles. Your human cells have organelles.)

Gene = a specific subunit of the chromosome that codes for a particular function. In fact there are other functions of genes besides making proteins, but our focus is on the way in which many of the genes carry the code — each for a specific protein — that causes cells to do their functions and coordinate their functions. That is, to be alive.

DNA = the molecule that carries the code of life from one generation of cells to another.

RNA = the molecule that translates the genetic code to make specific kinds of proteins.