ProteinsProteins

• Learning objectiveLearning objective

• To be able to describe the primary, To be able to describe the primary, secondary, tertiary and quarternary secondary, tertiary and quarternary structure of proteinsstructure of proteins

• In a protein the polypeptide chain may In a protein the polypeptide chain may be hundreds of amino acids long. be hundreds of amino acids long.

• Amino acid polymerisation to form Amino acid polymerisation to form polypeptides is part of polypeptides is part of protein protein synthesissynthesis..

• It takes place in ribosomes, and is It takes place in ribosomes, and is special because it requires an RNA special because it requires an RNA template. template.

• The sequence of amino acids in a The sequence of amino acids in a polypeptide chain is determined by the polypeptide chain is determined by the sequence of the genetic code in DNA. sequence of the genetic code in DNA.

Protein StructureProtein Structure

• Polypeptides are just a string of amino Polypeptides are just a string of amino acids, acids,

• They fold up to form the complex and They fold up to form the complex and well-defined three-dimensional well-defined three-dimensional structure of working proteins. structure of working proteins.

• To help to understand protein To help to understand protein structure, it is broken down into four structure, it is broken down into four levels:levels:

Primary StructurePrimary Structure

• This is just the sequence of amino acids in This is just the sequence of amino acids in the polypeptide chain, so is not really a the polypeptide chain, so is not really a structure at all. structure at all.

• However, the primary structure does However, the primary structure does determine the rest of the protein structure. determine the rest of the protein structure.

• Finding the primary structure of a protein is Finding the primary structure of a protein is called called protein sequencingprotein sequencing, and the first , and the first protein to be sequenced was the protein protein to be sequenced was the protein hormone insulin, by the Cambridge hormone insulin, by the Cambridge biochemist Fredrick Sanger, for which work biochemist Fredrick Sanger, for which work he got the Nobel prize in 1958.he got the Nobel prize in 1958.

Secondary StructureSecondary Structure

• Interactions between the R groups of Interactions between the R groups of the amino acids in the chain cause the the amino acids in the chain cause the chain to twist and fold into a three chain to twist and fold into a three dimensional shapedimensional shape

• Lengths of the chain may first coil into Lengths of the chain may first coil into αα-helices-helices or or ββ-pleated sheets-pleated sheets..

• These are known as the secondary These are known as the secondary structures.structures.

αα-helices-helices

• Within the helix, hydrogen bonds form Within the helix, hydrogen bonds form between the C=O of the carboxylic acid between the C=O of the carboxylic acid group and the NH of the amine group of group and the NH of the amine group of the different amino acids.the different amino acids.

ββ--sheetssheets

• Several chains may link together with Several chains may link together with hydrogen bonds holding the parallel hydrogen bonds holding the parallel chains together.chains together.

N C CO

H

N C CO

H

N C CO

H

N C CO

H

N C CO

H

C C NO

H

C C NO

H

C C NO

H

C C NO

H

C C NO

H

N

C

C

O

H

Tertiary structureTertiary structure• The polypeptide chain often folds and bends to The polypeptide chain often folds and bends to

produce a three dimensional shapeproduce a three dimensional shape• The tertiary structure is held together by bonds The tertiary structure is held together by bonds

between the R groups of the amino acids in the between the R groups of the amino acids in the protein, and so depends on what the sequence of protein, and so depends on what the sequence of amino acids is. There are three kinds of bonds amino acids is. There are three kinds of bonds involved:involved:– hydrogen bondshydrogen bonds, which are weak., which are weak.– ionic bondsionic bonds between R-groups with positive or between R-groups with positive or

negative charges, which are quite strong.negative charges, which are quite strong.– sulphur bridgessulphur bridges - covalent S-S bonds between - covalent S-S bonds between

two cysteine amino acids, which are strong.two cysteine amino acids, which are strong.

• The secondary structure is due to The secondary structure is due to backbone interactions and is thus backbone interactions and is thus largely independent of primary largely independent of primary sequence.sequence.

• The tertiary structure is due to side The tertiary structure is due to side chain interactions and thus depends on chain interactions and thus depends on the amino acid sequencethe amino acid sequence

Quaternary StructureQuaternary Structure

• This structure is found in proteins containing This structure is found in proteins containing more than one polypeptide chain, and simply more than one polypeptide chain, and simply means how the different polypeptide chains means how the different polypeptide chains are arranged together. are arranged together.

• The individual polypeptide chains are usually The individual polypeptide chains are usually globular, but can arrange themselves into a globular, but can arrange themselves into a variety of quaternary shapes. variety of quaternary shapes.

Globular and fibrous proteinsGlobular and fibrous proteins

• Proteins can be divided into two Proteins can be divided into two distinct groupsdistinct groups

Globular proteinsGlobular proteins

• The polypeptide chain is folded into a The polypeptide chain is folded into a compact spherical shapecompact spherical shape

• These proteins are soluble due to These proteins are soluble due to hydrophilic side chains that project hydrophilic side chains that project from the outside of the moleculesfrom the outside of the molecules

• Globular proteins are therefore Globular proteins are therefore important in metabolic reactionsimportant in metabolic reactions

Globular proteinsGlobular proteins

• Enzymes – 3D shape gives the ability to Enzymes – 3D shape gives the ability to form enzyme – substrate complexes form enzyme – substrate complexes and catalyse reactionsand catalyse reactions

• Transport proteins – 3D shape allows Transport proteins – 3D shape allows them to bind with other molecules eg: them to bind with other molecules eg: proteins in cell membranes or proteins in cell membranes or haemoglobin in red blood cells.haemoglobin in red blood cells.

• Antibodies – precise shape binds to Antibodies – precise shape binds to microorganismsmicroorganisms

Fibrous proteinsFibrous proteins

• These do not fold into a ball shapeThese do not fold into a ball shape

• They remain in long chains, often with They remain in long chains, often with several polypeptide chains cross linked several polypeptide chains cross linked together for additional strengthtogether for additional strength

• They are insolubleThey are insoluble

Fibrous proteinsFibrous proteins

• Keratin – in hair and skinKeratin – in hair and skin

• Collagen – in the skin, tendons, Collagen – in the skin, tendons, cartilage and blood vessel wallscartilage and blood vessel walls

Types of proteins

• Fibrous proteins– e.g. collagen– Insoluble– structural

• Globular proteins– e.g.enzymes– Soluble – 3D shape

Tertiary structureTertiary structure

• Bonding between R-groups Bonding between R-groups gives rise to a 3D shapegives rise to a 3D shape

• H-bonds =O HN-H-bonds =O HN-

• Ionic bonds –NHIonic bonds –NH33--COO-COO-

• Disulphide bridgeDisulphide bridge

--CH--CH22SS--SCHSCH22--

affected by temp & pHaffected by temp & pH

affected by pHaffected by pH

affected by reducing agentsaffected by reducing agents

Examples of Quaternary Examples of Quaternary StructureStructuress

• HaemoglobinHaemoglobin, the , the oxygen-carrying oxygen-carrying protein in red blood protein in red blood cells, consists of four cells, consists of four globular subunits globular subunits arranged in a arranged in a tetrahedral (pyramid) tetrahedral (pyramid) structure. structure.

• Each subunit Each subunit contains one iron contains one iron atom and can bind atom and can bind one molecule of one molecule of oxygen.oxygen.

Examples of Quaternary Examples of Quaternary StructureStructuress

• ImmunoglobulinsImmunoglobulins, the , the proteins that make proteins that make antibodies, comprise antibodies, comprise four polypeptide four polypeptide chains arranged in a chains arranged in a Y-shape. Y-shape.

• The chains are held The chains are held together by sulphur together by sulphur bridges. This shape bridges. This shape allows antibodies to allows antibodies to link antigens link antigens together, causing together, causing them to clump.them to clump.

Examples of Quaternary Examples of Quaternary StructureStructuress

• ActinActin, one of the proteins found in , one of the proteins found in muscles, consists of many globular muscles, consists of many globular subunits arranged in a double helix to subunits arranged in a double helix to form long filaments.form long filaments.

Just to be awkward… Just to be awkward…

• A few proteins have both structures: A few proteins have both structures: the muscle protein myosin has a long the muscle protein myosin has a long fibrous tail and a globular head, which fibrous tail and a globular head, which acts as an enzymeacts as an enzyme

• This diagram This diagram shows a molecule shows a molecule of the enzyme of the enzyme dihydrofolate dihydrofolate reductase, which reductase, which comprises a single comprises a single polypeptide chain. polypeptide chain. It has been drawn It has been drawn to highlight the to highlight the different secondary different secondary structures.structures.

• Can you identify Can you identify which is which?which is which?

1.1. ββ sheet sheet2.2. αα – helix – helix3.3. αα – helix – helix

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Questions Questions 1.1. Name the elements found in proteins.Name the elements found in proteins.2.2. What are the monomers of proteins?What are the monomers of proteins?3.3. Draw the structure of an amino acid (label the Draw the structure of an amino acid (label the

groups).groups).4.4. What is the name for the bond between two amino What is the name for the bond between two amino

acids?acids?5.5. What bonds are found in the secondary structure What bonds are found in the secondary structure

of proteins?of proteins?6.6. What is the test for protein?What is the test for protein?7.7. List 6 functions of proteins.List 6 functions of proteins.8.8. What is hydrolysis?What is hydrolysis?9.9. What is denaturation?What is denaturation?10.10. What kind of protein is an enzyme?What kind of protein is an enzyme?11.11. What is the function of a fibrous protein?What is the function of a fibrous protein?

Answers Answers 1.1. Name the elements found in proteins.Name the elements found in proteins.

• CHONSCHONS2.2. What are the monomers of proteins?What are the monomers of proteins?

• Amino acidsAmino acids3.3. Draw the structure of an amino acid (label the Draw the structure of an amino acid (label the

groups).groups).

carboxylic acid group

amine group

C

C

R

OO

NH

H

H

H

The group that determines what amino

acid is

4.4. What is the name for the bond between two amino What is the name for the bond between two amino acids?acids?

• PeptidePeptide

5.5. What bonds are found in the secondary structure What bonds are found in the secondary structure of proteins?of proteins?

• Hydrogen bondsHydrogen bonds

6.6. What is the test for protein?What is the test for protein?• Biuret test gives purple with proteinBiuret test gives purple with protein

7.7. List 6 functions of proteins.List 6 functions of proteins.• Enzymes, structural, carriers, pumps, hormones, Enzymes, structural, carriers, pumps, hormones,

antibodiesantibodies

8.8. What is hydrolysis?What is hydrolysis?• Breakdown of a substance by adding waterBreakdown of a substance by adding water

9.9. What is denaturation?What is denaturation?• Altering the shape of a proteinAltering the shape of a protein

10.10. What kind of protein is an enzyme?What kind of protein is an enzyme?• GlobularGlobular

11.11. What is the function of a fibrous protein?What is the function of a fibrous protein?• StructuralStructural