Globular Proteins
From Proteopedia
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| - | Globular proteins have a 3D molecular structure that has a shape that is anywhere from a sphere to a cigar. Usually the structure of a globular protein is divided into three or four levels. The primary structure is simply the sequence of amino acids forming the peptide chain. The peptide chain can be folded in an ordered and repetitive fashion, and the structures with repetitive conformations are called [[Secondary_structure|secondary structures]]. Three important types of secondary structures are [[Helices_in_Proteins|helices]], [[Sheets in Proteins|β-sheets]] and [[Turns in Proteins|turns]]. The tertiary structure is the overall 3D structure of a protein molecule and is produced by folding the helices and sheets upon themselves, and in the process of this folding turns and [[Loops in Proteins|loops]] are formed. Some globular proteins have a quaternary structure, and it is formed when two or more globular protein molecules (monomer) join together and form a multimeric unit. [[Hemoglobin]] is a good example of a protein that has a quarternary structure. | + | Globular proteins have a 3D molecular structure that has a shape that is anywhere from a sphere to a cigar. Usually the structure of a globular protein is divided into three or four levels. The primary structure is simply the sequence of amino acids forming the peptide chain. The peptide chain can be folded in an ordered and repetitive fashion, and the structures with repetitive conformations are called [[Secondary_structure|secondary structures]]. Three important types of secondary structures are [[Helices_in_Proteins|helices]], [[Sheets in Proteins|β-sheets]] and [[Turns in Proteins|turns]]. The tertiary structure is the overall 3D structure of a protein molecule and is produced by folding the helices and sheets upon themselves, and in the process of this folding turns and [[Loops in Proteins|loops]] are formed. Some globular proteins have a quaternary structure, and it is formed when two or more globular protein molecules (monomer) join together and form a multimeric unit. [[Hemoglobin]] is a good example of a protein that has a quarternary structure. The tertiary structure of many globular proteins can be characterized by the number of layers of peptide backbone which are present and the attractive forces which are generated by these layers.<ref name='Garret'>Biochemistry, 4th ed., R. H. Garrett & C. M. Grisham, Thomson/Brooks/Cole, pages 167-170.</ref> Other globular proteins are mainly characterized by the presence of disulfice bonds, the presence of chelated metal ions or that they are intrinsically unstructured<ref name='Garret'/>. The objective of this page is to introduce the tertiary structures of globular proteins by illustrating these characteristics of globular proteins. |
== Layers of Backbone Present in the Structure == | == Layers of Backbone Present in the Structure == | ||
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The five layers are <scene name='Globular_Proteins/Five_layers_identified/2'>identified</scene> in colors <font color="brown"><b>Brown</b></font> through <font color="#ff0000"><b>Red</b></font>. Display<scene name='Globular_Proteins/Five_layers_phobic/1'> hydrophobic residues</scene>; it is not as obvious as with the previous proteins, but as the structure rotates one can see that most of the spheres are in the interior between the layers. Looking at the <scene name='Globular_Proteins/Five_layers_polar/1'>polar residues</scene>, as it rotates one can observe more spheres on the edges of the structure than were seen in the previous scene. | The five layers are <scene name='Globular_Proteins/Five_layers_identified/2'>identified</scene> in colors <font color="brown"><b>Brown</b></font> through <font color="#ff0000"><b>Red</b></font>. Display<scene name='Globular_Proteins/Five_layers_phobic/1'> hydrophobic residues</scene>; it is not as obvious as with the previous proteins, but as the structure rotates one can see that most of the spheres are in the interior between the layers. Looking at the <scene name='Globular_Proteins/Five_layers_polar/1'>polar residues</scene>, as it rotates one can observe more spheres on the edges of the structure than were seen in the previous scene. | ||
| - | === | + | === Other Examples === |
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| - | + | ==== α-Helix Predominate ==== | |
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The peptides in this class have a high contain of α-helix and because of the loops and turns which are present the α-helical strands will be antiparallel with respect to their adjacent strands. The examples which follow are colored N-C rainbow so that the N-terminus and C-terminus of the α-helices can be determined. The amino end of the protein starts with <font color="#0000ff"><b>Blue</b></font>, and moving to the carboxyl end of the peptide the coloration proceeds through the colors of the rainbow and ends with <font color="#ff0000"><b>Red</b></font>. Comparing the colors which are present at the ends of a helical strand one can determine which is the N-terminus and C-terminus, and thereby determine if adjacent helices are parallel or antiparallel. | The peptides in this class have a high contain of α-helix and because of the loops and turns which are present the α-helical strands will be antiparallel with respect to their adjacent strands. The examples which follow are colored N-C rainbow so that the N-terminus and C-terminus of the α-helices can be determined. The amino end of the protein starts with <font color="#0000ff"><b>Blue</b></font>, and moving to the carboxyl end of the peptide the coloration proceeds through the colors of the rainbow and ends with <font color="#ff0000"><b>Red</b></font>. Comparing the colors which are present at the ends of a helical strand one can determine which is the N-terminus and C-terminus, and thereby determine if adjacent helices are parallel or antiparallel. | ||
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Did you notice that the backbones of all of these can be divided into two layers? | Did you notice that the backbones of all of these can be divided into two layers? | ||
| - | === | + | ==== β-Sheets Predominate ==== |
| + | * <scene name='Globular_Proteins/St_inhibitor/1'>Soybean trypsin inhibitor</scene> - As its name implies this protein inhibits the enzyme trypsin, and this inhibitory effect must be deactivated in the process of preparing soybeans for use in animal feed, so that the proteins in soybeans are hydrolyzed by trypsin. This protein is an example of the antiparallel β-barrel, and as you can see it is not as clearly defined as the parallel β-barrel, but you can look through the barrel whenever one of the open ends rotates to face the screen. Notice that an outer layer of α-helices is not present like it is in the parallel β-barrel. | ||
| + | * <scene name='Globular_Proteins/Concan/1'>Concanavalin</scene> - Example of a lectin, plasma membrane proteins that bind oligsaccharides and glycoproteins and are involved in cell-cell recognition. There are two antiparallel β-sheets, and the hydrophobic sides of the sheets are facing each other. They are interlocking β-Sheets or have Greek Key Topology. Observe that after laying down a strand in a sheet, often the peptide chain loops over to the other sheet and lays down a strand in that sheet. | ||
| + | * <scene name='Globular_Proteins/Crystallin/1'>Gamma-Crystallin</scene> - A protein that is a component of the eye lense. Look closely and you will see that this protein is another example of interlocking β-sheet, two of the Greek key bilayers are connected by a looping peptide segment. | ||
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In addition to having pure parallel β-sheets, some of the proteins in this class contain a β-sheet that has one or two antiparallel strands giving a mixed β-sheet. A characteristic of parallel β-sheets is that both sides of the sheet have hydrophpbic side chains<ref name='Garret'/>. A consequence of this is that parallel or mixed β-sheets must be located in the interior of the molecule. This type of sheet can not be on the surface exposing the hydrophobic chains to water. | In addition to having pure parallel β-sheets, some of the proteins in this class contain a β-sheet that has one or two antiparallel strands giving a mixed β-sheet. A characteristic of parallel β-sheets is that both sides of the sheet have hydrophpbic side chains<ref name='Garret'/>. A consequence of this is that parallel or mixed β-sheets must be located in the interior of the molecule. This type of sheet can not be on the surface exposing the hydrophobic chains to water. | ||
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| + | ==== Mixture of α-helix and β-Sheet ==== | ||
| + | In the peptides of this class side-by-side strands of a β-sheet run in opposite directions. One side of the sheet will have polar side chains projecting from it, and the other side will have hydrophobic chains. The polar side of the sheet can be on the surface of the molecule, but the hydrophobic side must be covered with another nonpolar layer of side chains. Peptides in this class can have as few as two layers of backbone. The examples given below show the hydrophobic layer being covered in different ways. One of these methods result in a barrel or cylindrical shape. The barrel formed by the parallel β-sheet, as seen above, is more symmetrical, but the antiparallel β-barrel is more common. A second way is to cover the hydrophobic sheet with a layer of backbone made up of α-helices and extended loops. The third way is to form two interlocking antiparallel β-sheets or Greek Key Topology. The sheets are interlocking in the sense that after laying down an antiparallel strand in one sheet the peptide chain loops over and lays down an antiparallel strand in the opposing sheet. | ||
* <scene name='Globular_Proteins/Tp_isomerase/1'>Triose phosphate isomerase</scene> - The β-sheet of the barrel is parallel because after forming a strand of the sheet the peptide chain loops out, forms an α-helix and then loops back to form another strand of the sheet running in the same direction as the previous strand and, thereby, making the sheet parallel. Find the four layers of backbone in this example. | * <scene name='Globular_Proteins/Tp_isomerase/1'>Triose phosphate isomerase</scene> - The β-sheet of the barrel is parallel because after forming a strand of the sheet the peptide chain loops out, forms an α-helix and then loops back to form another strand of the sheet running in the same direction as the previous strand and, thereby, making the sheet parallel. Find the four layers of backbone in this example. | ||
* <scene name='Globular_Proteins/Flavodxin/1'>Flavodoxin</scene> - This type of structure is also called doubly wound parallel β-sheet because of the loops of α-helices on both sides of the sheet. In some cases these doubly wound sheets contain a few antiparallel strands forming a mixed β-sheet. Can you find the three layers of backbone in these doubly wound sheets contain? | * <scene name='Globular_Proteins/Flavodxin/1'>Flavodoxin</scene> - This type of structure is also called doubly wound parallel β-sheet because of the loops of α-helices on both sides of the sheet. In some cases these doubly wound sheets contain a few antiparallel strands forming a mixed β-sheet. Can you find the three layers of backbone in these doubly wound sheets contain? | ||
* <scene name='Globular_Proteins/Pg_mutase/1'>Phosphoglycerate mutase</scene> - There is one antiparallel strand in the sheet making it a mixed β-sheet, and the double winding is more extensive. | * <scene name='Globular_Proteins/Pg_mutase/1'>Phosphoglycerate mutase</scene> - There is one antiparallel strand in the sheet making it a mixed β-sheet, and the double winding is more extensive. | ||
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* <scene name='Globular_Proteins/Rubredoxin/1'>Rubredoxin</scene> - Redoxins are sufhydryl containing proteins that participate in redox reactions. Another example of a β-Barrel, in this case α-helices and loops help form the shape of the barrel. The α-helices aid in covering the hydrophobic side of the sheet. | * <scene name='Globular_Proteins/Rubredoxin/1'>Rubredoxin</scene> - Redoxins are sufhydryl containing proteins that participate in redox reactions. Another example of a β-Barrel, in this case α-helices and loops help form the shape of the barrel. The α-helices aid in covering the hydrophobic side of the sheet. | ||
* <scene name='Globular_Proteins/Subtilisin/1'>Subtilisin inhibitor</scene> - Subtilisin is a bacterial protease, and this protein is an inhibitor of this enzyme. β-Sheet covered with α-helices and loops: As the structure rotates you can see the two distinct layers, an antiparallel β-sheet and the hydrophobic side of this sheet covered with a layer made up of α-helices and loops. | * <scene name='Globular_Proteins/Subtilisin/1'>Subtilisin inhibitor</scene> - Subtilisin is a bacterial protease, and this protein is an inhibitor of this enzyme. β-Sheet covered with α-helices and loops: As the structure rotates you can see the two distinct layers, an antiparallel β-sheet and the hydrophobic side of this sheet covered with a layer made up of α-helices and loops. | ||
| - | + | </StructureSection> | |
| - | + | <table width='500' align='right' cellpadding='10'><tr><td bgcolor='#eeeeee'><center>'''Tertiary Structures of Examples'''<scene name='Globular_Proteins/Two_layers/2'> (Initial scene)</scene></center></td></tr></table> | |
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| + | <StructureSection load='2mhr' size='500' side='right' caption='' scene='Globular_Proteins/Anti_helix_erythrin/1'>__NOTOC__ | ||
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| + | === Non-stabilizing Layers === | ||
| + | Load <scene name='Globular_Proteins/Non_layers/1'>structure</scene>. Even though backbone layers can be identified in these molecular structures, the layers are not extensive enough and/or positioned well enough for the hydrophobic side chains to have significant interaction so the hydrophobic attractions do not make a major contribution to their stability. Display <scene name='Globular_Proteins/Non_layers_phobic/1'>hydrophobic residues</scene>. There are fewer hydrophobic side chains in the interior, and therefore weaker hydrophobic attraction, so the major force involved in maintaining the tertiary structure is the covalent Disulfide Bonds (yellow rods) which were not present in the examples covered above. As one would expect the <scene name='Globular_Proteins/Non_layers_polar/1'>polar side chains</scene> are plentiful on the surface of the protein. | ||
The metal-rich and disulfide-rich proteins have some characteristics in common. Some of the proteins in these two classes are small in size and therefore do not have large amounts of backbone that can be organized into layers. Others have significant layers of backbone, but the layers are not well organized, and therefore the side chain interactions are not strong. For the proteins in this class, the disulfide bonds or the bonds formed between metal ions and ligands are as important or more than the hydrophobic interactions of the side chains. | The metal-rich and disulfide-rich proteins have some characteristics in common. Some of the proteins in these two classes are small in size and therefore do not have large amounts of backbone that can be organized into layers. Others have significant layers of backbone, but the layers are not well organized, and therefore the side chain interactions are not strong. For the proteins in this class, the disulfide bonds or the bonds formed between metal ions and ligands are as important or more than the hydrophobic interactions of the side chains. | ||
Revision as of 14:19, 24 February 2011
Globular proteins have a 3D molecular structure that has a shape that is anywhere from a sphere to a cigar. Usually the structure of a globular protein is divided into three or four levels. The primary structure is simply the sequence of amino acids forming the peptide chain. The peptide chain can be folded in an ordered and repetitive fashion, and the structures with repetitive conformations are called secondary structures. Three important types of secondary structures are helices, β-sheets and turns. The tertiary structure is the overall 3D structure of a protein molecule and is produced by folding the helices and sheets upon themselves, and in the process of this folding turns and loops are formed. Some globular proteins have a quaternary structure, and it is formed when two or more globular protein molecules (monomer) join together and form a multimeric unit. Hemoglobin is a good example of a protein that has a quarternary structure. The tertiary structure of many globular proteins can be characterized by the number of layers of peptide backbone which are present and the attractive forces which are generated by these layers.[1] Other globular proteins are mainly characterized by the presence of disulfice bonds, the presence of chelated metal ions or that they are intrinsically unstructured[1]. The objective of this page is to introduce the tertiary structures of globular proteins by illustrating these characteristics of globular proteins.
Layers of Backbone Present in the Structure
Layers of backbone in the core of the structure is a feature that many, but not all, globular proteins have. The number of layers and their location vary for different proteins, but, in all case that have layers, the hydrophobic forces between the layers play a major role in maintaining the tertiary structure.
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References
PDB Files Used
1a7v, 1php, 8tim, 1abb, 2bp2, 2mhr, 1vtm, 1mbo, 1czn, 1e59, 1avu, 5rxn, 3ssi, 1scr, 1elp, 1ben, 1jxu
