Proteins

proteins media type="file" key="protein r b s.m4a" width="278" height="278" Ryan Sean Brad

Proteins Proteins are macromolecules. They are constructed from one or more unbranched chains of amino acids; that is, they are polymers. A typical protein contains 200–300 amino acids but some are much smaller (the smallest are often called peptides) and some much larger (the largest to date is titin a protein found in skeletal and cardiac muscle; it contains 26,926 amino acids in a single chain!).

Link to a discussion of how the amino acids are linked together.

Every function in the living cell depends on proteins.

•Motion and locomotion of cells and organisms depends on contractile proteins. [Examples: Muscles] •The catalysis of all biochemical reactions is done by enzymes, which contain protein. •The structure of cells, and the extracellular matrix in which they are embedded, is largely made of protein. [Examples: Collagens] (Plants and many microbes depend more on carbohydrates, e.g., cellulose, for support, but these are synthesized by enzymes.) •The transport of materials in body fluids depends of proteins. [See Blood] •The receptors for hormones and other signaling molecules are proteins. •Proteins are an essential nutrient for heterotrophs. •The transcription factors that turn genes on and off to guide the differentiation of the cell and its later responsiveness to signals reaching it are proteins. •and many more — proteins are truly the physical basis of life. The protein represented here displays many of the features of proteins. Let's examine some of them as you scroll down the image.

The protein consists of two polypeptide chains, a long one on the left of 346 amino acids — it is called the heavy chain — and a short one on the right of 99 amino acids.

The heavy chain is shown as consisting of 5 main regions or domains: •three extracellular domains, designated here as N (includes the N-terminal), C1, and C2; •a transmembrane domain where the polypeptide chain passes through the plasma membrane of the cell; •a cytoplasmic domain (with the C terminal) within the cytoplasm of the cell. Because it is anchored in the plasma membrane of the cell, the heavy chain is called an integral membrane protein.

To the right is the protein molecule called beta-2 microglobulin. It is not attached to the heavy chain by any covalent bonds, but rather by a number of noncovalent interactions like hydrogen bonds. Proteins associated noncovalently with integral membrane proteins are called peripheral membrane proteins.

Link to a color diagram showing the relationship between integral and peripheral membrane proteins (48K)

The dark bars represent disulfide (S-S) bridges linking portions of each external domain (except the N domain). However, the bonds in S-S bridges are no longer than any other covalent bond, so if this molecule could be viewed in its actual tertiary (3D) configuration, we would find that the portions of the polypeptide chains containing the linked Cys are actually close together.

Link to a color model showing this (92K). But note that the terminology for the domains is different in this model: N = alpha1, C1 = alpha2, C2 = alpha 3

The two objects on the left of the image that look like candelabra represent short, branched chains of sugars. The base of each is attached to an asparagine (N). Proteins with covalently linked carbohydrate are called glycoproteins. When the carbohydrate is linked to asparagine, it is said to be "N-linked".

The presence of sugars on the molecule makes this region hydrophilic as befits its location projecting into the fluid that surrounds the cell. The amino acids exposed at the surface of the extracellular domains tend to be hydrophilic as well.

However, most of the amino acids in the transmembrane domain are hydrophobic, as befits their hydrophobic surroundings.

Most of the amino acids in the cytoplasmic domain are hydrophilic, which is appropriate for the aqueous medium of the cytosol, but carbohydrate is not found in the intracellular domains of integral membrane proteins.

The regions marked "Papain" represent the places on the long chain that are attacked by the proteinase papain (and made it possible to release the extracellular domains from the plasma membrane for easier analysis).

This molecule represents a "single-pass" transmembrane protein; the polypeptide chain traverses the plasma membrane once only. However, many transmembrane proteins pass through several, but always a precisely defined number, of times.

This image (courtesy of T.J. Kindt and J. E. Coligan) represents the structure of a class I histocompatibility molecule, called H-2K. Almost all the cells of an animal's body (in this case, a mouse) have thousands of these molecules present in their plasma membrane. These molecules provide tissue identity and serve as major targets in the rejection of transplanted tissue and organs. Hence molecules of this type are often called transplantation antigens. But tissue rejection is not their natural function. Class I molecules serve to display antigens on the surface of the cell so that they can be "recognized" by T cells.

Discussion of antigen presentation by class I molecules

Protein Synthesis When proteins are first synthesized, a process called translation, they consist of a linear assembly of the various amino acids, of which only 20 are normally used.

Translation: How proteins are synthesized using the genetic code.

Post-Translational Modifications of Protein Structure Later, "post-translational" steps can alter some of the amino acids by covalent attachment of •a variety of sugar residues to form glycoproteins (like the molecule above); •phosphate groups, on Tyr for example. The adding of phosphate groups (by kinases) and their removal (by phosphatases) are crucial to the control of the function of many proteins. [Link to examples.] •sulfate groups (SO42-) can also be covalently attached to Tyr residues. Circular Proteins Some bacteria, plants, and animals (but not humans) cut one or more peptides out of certain of their translated proteins and link the free ends together to form a circular protein. The details of how this is done are not yet known, but with a free amino group and one end and a free carboxyl at the other (the groups that form all peptide bonds) there is no chemical difficulty to overcome. The advantage of circular proteins seems to be great resistance to degradation (e.g., no free end for peptidases to work on).

Inteins Another, very rare, post-translational modification is the later removal of a section of the polypeptide and the splicing together (with a peptide bond) of the remaining N-terminal and C-terminal segments. The portion removed is called an intein (a "protein intron") and the ligated segments are called exteins ("protein exons").

Genes encoding inteins have been discovered in a variety of organisms, including •some "true" bacteria such as ◦Bacillus subtilis ◦several mycobacteria ◦several blue-green algae (cyanobacteria) •some Archaea such as ◦Methanococcus jannaschii ◦Aeropyrum pernix •and a few eukaryotes, e.g., budding yeast (Saccharomyces cerevisiae). •None has been found in the genomes of higher eukaryotes like Drosophila, C. elegans, or the green plant Arabidopsis. http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/Proteins.html

hey guys i found a great site about proteins, its way to much info to copy and past like i did with the stuff above so im just gonna give the link, but its a really good site that goes into detail about proteins, the site is http://www.friedli.com/herbs/phytochem/proteins.html

__Protein Structure__ Proteins are polymers of amino acids covalently linked through peptide bonds into a chain. Proteins are polymers of amino acids joined together by peptide bonds. There are 20 different amino acids that make up essentially all proteins on earth. Each of these amino acids has a fundamental design http://www.vivo.colostate.edu/hbooks/genetics/biotech/basics/prostruct.html
 * a hydrogen
 * a carboxyl group
 * an amino group
 * a unique side chain or R-group
 * each R group is different and identifies each amino acid
 * it also gives the chemical properties of each amino acid

1. Introduction
Proteins are generally regarded as beneficial, and are a necessary part of the diet of all animals. Humans can become seriously ill if they do not eat enough suitable protein, the disease //kwashiorkor// being an extreme form of protein deficiency. Protein based antibiotics and vaccines help to fight disease, and we warm and protect our bodies with clothing and shoes that are often protein in nature (e.g. wool, silk and leather). The deadly properties of protein toxins and venoms is less widely appreciated. Botulinum toxin A, from //Clostridium botulinum//, is regarded as the most powerful poison known. Based on toxicology studies, a teaspoon of this toxin would be sufficient to kill a fifth of the world's population. The toxins produced by tetanus and diphtheria microorganisms are nearly as poisonous. A list of highly toxic proteins or peptides would also include the venoms of many snakes, and ricin, the toxic protein found in castor beans. Despite the variety of their physiological function and differences in physical properties--silk is a flexible fiber, horn a tough rigid solid, and the enzyme pepsin water soluble crystals--proteins are sufficiently similar in molecular structure to warrant treating them as a single chemical family. When compared with carbohydrates and lipids, the proteins are obviously different in fundamental composition. The lipids are largely hydrocarbon in nature, generally being 75 to 85% carbon. Carbohydrates are roughly 50% oxygen, and like the lipids, usually have less than 5% nitrogen (often none at all). Proteins and peptides, on the other hand, are composed of 15 to 25% nitrogen and about an equal amount of oxygen. The distinction between proteins and peptides is their size. Peptides are in a sense small proteins, having molecular weights less than 10,000. 
 * Proteins**, from the Greek //proteios//, meaning first, are a class of organic compounds which are present in and vital to every living cell. In the form of skin, hair, callus, cartilage, muscles, tendons and ligaments, proteins hold together, protect, and provide structure to the body of a multicelled organism. In the form of enzymes, hormones, antibodies, and globulins, they catalyze, regulate, and protect the body chemistry. In the form of hemoglobin, myoglobin and various lipoproteins, they effect the transport of oxygen and other substances within an organism.
 * ~ ==== α-Amino Acids ==== || ==== ==== ||

2. Natural α-Amino Acids
Hydrolysis of proteins by boiling aqueous acid or base yields an assortment of small molecules identified as α-aminocarboxylic acids. More than twenty such components have been isolated, and the most common of these are listed in the following table. Those amino acids having green colored names are **essential** diet components, since they are not synthesized by human metabolic processes. The best food source of these nutrients is protein, but it is important to recognize that not all proteins have equal nutritional value. For example, peanuts have a higher weight content of protein than fish or eggs, but the proportion of essential amino acids in peanut protein is only a third of that from the two other sources. For reasons that will become evident when discussing the structures of proteins and peptides, each amino acid is assigned a one or three letter abbreviation.   Some common features of these amino acids should be noted. With the exception of proline, they are all 1º-amines; and with the exception of glycine, they are all chiral. The configurations of the chiral amino acids are the same when written as a Fischer projection formula, as in the drawing on the right, and this was defined as the **L-configuration** by [|Fischer]. The R-substituent in this structure is the remaining structural component that varies from one amino acid to another, and in proline R is a three-carbon chain that joins the nitrogen to the alpha-carbon in a five-membered ring. Applying the [|Cahn-Ingold-Prelog notation], all these natural chiral amino acids, with the exception of cysteine, have an **S**-configuration. For the first seven compounds in the left column the R-substituent is a hydrocarbon. The last three entries in the left column have hydroxyl functional groups, and the first two amino acids in the right column incorporate thiol and sulfide groups respectively. Lysine and arginine have basic amine functions in their side-chains; histidine and tryptophan have less basic nitrogen heterocyclic rings as substituents. Finally, carboxylic acid side-chains are substituents on aspartic and glutamic acid, and the last two compounds in the right column are their corresponding amides. The formulas for the amino acids written above are simple covalent bond representations based upon previous understanding of mono-functional analogs. **The formulas are in fact incorrect**. This is evident from a comparison of the physical properties listed in the following table. All four compounds in the table are roughly the same size, and all have moderate to excellent water solublility. The first two are simple carboxylic acids, and the third is an amino alcohol. All three compounds are soluble in organic solvents (e.g. ether) and have relatively low melting points. The carboxylic acids have pKa's near 4.5, and the conjugate acid of the amine has a pKa of 10. The simple amino acid alanine is the last entry. By contrast, it is very high melting (with decomposition), insoluble in organic solvents, and a million times weaker as an acid than ordinary carboxylic acids.  in Water ||~ Solubility in Ether ||~ Melting Point ||~ pKa || Show Spacefill Model Show Stick Model Show Tyrosine Show Cysteine Show Lysine Show Aspartic Acid ||  ||
 * ~ === Natural α-Amino Acids === ||
 * ~ [[image:http://www.cem.msu.edu/%7Ereusch/VirtualText/Images3/aminacid.gif]] ||
 * ====Physical Properties of Selected Acids and Amines==== ||~ Compound ||~ Formula ||~ Mol.Wt. ||~ Solubility
 * isobutyric acid || (CH3)2CHCO2H || 88 || 20g/100mL || complete || -47 ºC || 5.0 ||
 * lactic acid || CH3CH(OH)CO2H || 90 || complete || complete || 53 ºC || 3.9 ||
 * 3-amino-2-butanol || CH3CH(NH2)CH(OH)CH3 || 89 || complete || complete || 9 ºC || 10.0 ||
 * alanine || CH3CH(NH2)CO2H || 89 || 18g/100mL || insoluble || ca. 300 ºC || 9.8 ||  ||   ||   ||
 * Show Zwitterionic Form

These differences all point to internal salt formation by a proton transfer from the acidic carboxyl function to the basic amino group. The resulting ammonium carboxylate structure, commonly referred to as a **zwitterion**, is also supported by the spectroscopic characteristics of alanine. As expected from its ionic character, the alanine zwitterion is high melting, insoluble in nonpolar solvents and has the acid strength of a 1º-ammonium ion. To the right above is a Jmol display of an L-amino acid. The model will change to its zwitterionic form by clicking the appropriate button beneath the display. Examples of a few specific amino acids may also be viewed in their favored neutral zwitterionic form. Note that in lysine the amine function farthest from the carboxyl group is more basic than the alpha-amine. Consequently, the positively charged ammonium moiety formed at the chain terminus is attracted to the negative carboxylate, resulting in a coiled conformation.  Since amino acids, as well as peptides and proteins, incorporate both acidic and basic functional groups, the predominant molecular species present in an aqueous solution will depend on the pH of the solution. In order to determine the nature of the molecular and ionic species that are present in aqueous solutions at different pH's, we make use of the **Henderson-Hasselbach Equation**, written below. Here, the pKa represents the acidity of a specific conjugate acid function (HA). When the pH of the solution equals pKa, the concentrations of HA and A(-) must be equal (log 1 = 0). The titration curve for alanine, shown below, demonstrates this relationship. At a pH lower than 2, both the carboxylate and amine functions are protonated, so the alanine molecule has a net positive charge. At a pH greater than 10, the amine exists as a neutral base and the carboxyl as its conjugate base, so the alanine molecule has a net negative charge. At intermediate pH's the zwitterion concentration increases, and at a characteristic pH, called the **isoelectric point** (**pI**), the negatively and positively charged molecular species are present in equal concentration. This behavior is general for simple (difunctional) amino acids. Starting from a fully protonated state, the pKa's of the acidic functions range from 1.8 to 2.4 for -CO2H, and 8.8 to 9.7 for -NH3(+). The isoelectric points range from 5.5 to 6.2. Titration curves show the neutralization of these acids by added base, and the change in pH during the titration. Titration curves for many other amino acids may be examined at a useful site provided by [|The University of Virginia in Charlottesville]. (Click this name)  The distribution of charged species in a sample can be shown experimentally by observing the movement of solute molecules in an electric field, using the technique of **electrophoresis**. For such experiments an ionic buffer solution is incorporated in a solid matrix layer, composed of paper or a crosslinked gelatin-like substance. A small amount of the amino acid, peptide or protein sample is placed near the center of the matrix strip and an electric potential is applied at the ends of the strip, as shown in the following diagram. The solid structure of the matrix retards the diffusion of the solute molecules, which will remain where they are inserted, unless acted upon by the electrostatic potential. In the example shown here, four different amino acids are examined simultaneously in a pH 6.00 buffered medium. To see the result of this experiment, click on the illustration. Note that the colors in the display are only a convenient reference, since these amino acids are colorless. At pH 6.00 alanine and isoleucine exist on average as neutral zwitterionic molecules, and are not influenced by the electric field. Arginine is a basic amino acid. Both base functions exist as "onium" conjugate acids in the pH 6.00 matrix. The solute molecules of arginine therefore carry an excess positive charge, and they move toward the cathode. The two carboxyl functions in aspartic acid are both ionized at pH 6.00, and the negatively charged solute molecules move toward the anode in the electric field. Structures for all these species are shown to the right of the display.  pKa1 ||~ α-NH3 pKa2 ||~ Side Chain pKa3 ||~ pI || It should be clear that the result of this experiment is critically dependent on the pH of the matrix buffer. If we were to repeat the electrophoresis of these compounds at a pH of 3.00, the aspartic acid would remain at its point of origin, and the other amino acids would move toward the cathode. Ignoring differences in molecular size and shape, the arginine would move twice as fast as the alanine and isoleucine because its solute molecules on average would carry a double positive charge. As noted earlier, the titration curves of simple amino acids display two inflection points, one due to the strongly acidic carboxyl group (pKa1 = 1.8 to 2.4), and the other for the less acidic ammonium function (pKa2 = 8.8 to 9.7). For the 2º-amino acid proline, pKa2 is 10.6, reflecting the greater basicity of 2º-amines. Some amino acids have additional acidic or basic functions in their side chains. These compounds are listed in the table on the right. A third pKa, representing the acidity or basicity of the extra function, is listed in the fourth column of the table. The pI's of these amino acids (last column) are often very different from those noted above for the simpler members. As expected, such compounds display three inflection points in their titration curves, illustrated by the titrations of arginine and aspartic acid shown below. For each of these compounds four possible charged species are possible, one of which has no overall charge. Formulas for these species are written to the right of the titration curves, together with the pH at which each is expected to predominate. The very high pH required to remove the last acidic proton from arginine reflects the [|exceptionally high basicity of the guanidine moiety] at the end of the side chain.
 * CH3CH(NH2)CO2H || [[image:http://www.cem.msu.edu/%7Ereusch/VirtualText/Images/arroweq1.gif]] || CH3CH(NH3) (+) CO2 (–) ||
 * [[image:http://www.cem.msu.edu/%7Ereusch/VirtualText/Images3/elephor1.gif link="javascript:chng1"]] ||  || [[image:http://www.cem.msu.edu/%7Ereusch/VirtualText/Images3/aacids60.gif]] ||
 * **pKa Values of Polyfunctional Amino Acids** ||~ Amino Acid ||~ α-CO2H
 * Arginine || 2.1 || 9.0 || 12.5 || 10.8 ||
 * Aspartic Acid || 2.1 || 9.8 || 3.9 || 3.0 ||
 * Cysteine || 1.7 || 10.4 || 8.3 || 5.0 ||
 * Glutamic Acid || 2.2 || 9.7 || 4.3 || 3.2 ||
 * Histidine || 1.8 || 9.2 || 6.0 || 7.6 ||
 * Lysine || 2.2 || 9.0 || 10.5 || 9.8 ||
 * Tyrosine || 2.2 || 9.1 || 10.1 || 5.7 ||  ||


 * [[image:http://www.cem.msu.edu/%7Ereusch/VirtualText/Images3/asptitr.gif]] ||
 * [[image:http://www.cem.msu.edu/%7Ereusch/VirtualText/Images3/argtitr.gif]] ||

3. The Isoelectric Point
[|As defined above], the isoelectric point, **pI**, is the pH of an aqueous solution of an amino acid (or peptide) at which the molecules on average have no net charge. In other words, the positively charged groups are exactly balanced by the negatively charged groups. For simple amino acids such as alanine, the pI is an average of the pKa's of the carboxyl (2.34) and ammonium (9.69) groups. Thus, the pI for alanine is calculated to be: (2.34 + 9.69)/2 = 6.02, the experimentally determined value. If additional acidic or basic groups are present as side-chain functions, the pI is the average of the pKa's of the two most similar acids. To assist in determining similarity we define two classes of acids. The first consists of acids that are neutral in their protonated form (e.g. CO2H & SH). The second includes acids that are positively charged in their protonated state (e.g. -NH3+). In the case of aspartic acid, the similar acids are the alpha-carboxyl function (pKa = 2.1) and the side-chain carboxyl function (pKa = 3.9), so pI = (2.1 + 3.9)/2 = 3.0. For arginine, the similar acids are the guanidinium species on the side-chain (pKa = 12.5) and the alpha-ammonium function (pKa = 9.0), so the calculated pI = (12.5 + 9.0)/2 = 10.75. 

4. Other Natural Amino Acids
The twenty alpha-amino acids [|listed above] are the primary components of proteins, their incorporation being governed by the genetic code. Many other naturally occuring amino acids exist, and the structures of a few of these are displayed below. Some, such as hydroxylysine and hydroxyproline, are simply functionalized derivatives of a previously described compound. These two amino acids are found only in [|collagen], a common structural protein. Homoserine and homocysteine are higher homologs of their namesakes. The amino group in beta-alanine has moved to the end of the three-carbon chain. It is a component of pantothenic acid, HOCH2C(CH3)2CH(OH)CONHCH2CH2CO2H, a member of the vitamin B complex and an essential nutrient. Acetyl coenzyme A is a pyrophosphorylated derivative of a pantothenic acid amide. The gamma-amino homolog GABA is a neurotransmitter inhibitor and antihypertensive agent.

Many unusual amino acids, including D-enantiomers of some common acids, are produced by microorganisms. These include ornithine, which is a component of the antibiotic bacatracin A, and statin, found as part of a pentapeptide that inhibits the action of the digestive enzyme **pepsin**. [|http://www.cem.msu.edu/~reusch/VirtualText/proteins.htm]

Brad, Ryan, Sean Podcast Script

Brad-Our group which consists of Brad Surette, Ryan Flannary and Sean Rider did our podcast on proteins.

Ryan- The dictionary definition of a protein is any of numerous, highly varied organic molecules constituting a large portion of the mass of every life form and necessary in the diet of all animals and other nonphotosynthesizing organisms, composed of 20 or more amino acids linked in a genetically controlled linear sequence into one or more long polypeptide chains, the final shape and other properties of each protein being determined by the side chains of the amino acids and their chemical attachments: proteins include such specialized forms as collagen for supportive tissue, hemoglobin for transport, antibodies for immune defense, and enzymes for metabolism.

Sean- This means that proteins are a class of organic compounds which are present in and vital to every living cell. In the form of skin, hair, callus, cartilage, muscles, tendons and ligaments, proteins hold together, protect, and provide structure to the body of a multicelled organism. In the form of enzymes, hormones, antibodies, and globulins, they catalyze, regulate, and protect the body chemistry. In the form of hemoglobin, myoglobin and various lipoproteins, they affect the transport of oxygen and other substances within an organism. Proteins are very beneficial to all living multicelled organisms, and there are many protein based vaccines and antibiotics that help fight diseases.

Brad- Proteins are polymers of amino acids that are linked into a chain covalently through peptide bonds. There are 20 different amino acids that make up pretty much all proteins on earth. Each of the amino acids has a similar design. They all have hydrogen, a carboxyl group, an amino group and a unique side chain or R-group. The R-group is what determines the type and characteristics of each protein.

Ryan- While proteins can be very beneficial to our lives they also can be very dangerous. Protein toxins and venons while not very appreciated are found in everyday life. Botulinum Toxin A is regarded as the most dangerous poison known to man. It is estimated that one teaspoon of the substance could kill one fifth of earth's popultion. The toxins in tethanus and diphtheria are also fatal at times. The venoms from snakes are also deadly protein toxins.  Sean- When compared with lipids and carbohydrates, proteins have distinct differences in fundmental structure. Lipids are hydrogcarbons and are generally 75 to 85% carbon usually 5% nitrogen. Carbohydrates are roughly 15 to 25% carbon with a very similar percentage of nitrogen. The distinction between proteins and peptides are their size. Peptide are usually smaller with a weight less than 10,000 units.  Brad- Proteins are an essential food source for living organisms. What makes them such a key part to our diet are the amino acids that come with it. Peanut Butter has a greater mass a protein than eggs or fish but only contains one third of the essential amino acids as the other two.  Ryan- Natural a Amino Acids have all the same characteristics to define them. Each is a 1 <span style="color: rgb(222, 123, 59);">° amine, and they are also all chiral. They are also all drawn in an L-configuration.

Sean Ryan Brad- The End

PICTURES http://www.masternewmedia.org/images/vaccines_injection.jpg

http://joeorman.shutterace.com/Wildlife/wildlife_rattlesnake1.jpg

http://expatbrazil.files.wordpress.com/2008/02/peanutbutter_skippy.jpg

http://midnightraider.typepad.com/photos/uncategorized/2007/10/04/fish.jpg

http://www.foodsubs.com/Photos/egg.jpg

http://scienceblogs.com/clock/upload/2006/11/a2%20animal%20cell.png

http://www.mcat45.com/images/Amino-Acid-MCAT.png

http://www.sccollege.edu/pic/558/graphicmuscles.jpg

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