Protein structure and function Higher Human Biology Sub topic 4 (a)

Learning Intentions Describe the different structures of proteins Describe different functions of proteins To discuss the effects of mutations in the code

Proteins are…. Made of the elements……. Long chains of amino acids. Joined by peptide bonds.

The structure of the protein determines its function!!!!!!

PROTEIN PRIMARY STRUCTURE The primary structure of a protein is the polypeptide chain of amino acids

PROTEIN SECONDARY STRUCTURE Weak hydrogen bonds form between various amino acids. This causes the polypeptide chain to become coiled into an  helix (coiled) or folded into a  pleated sheet (folded)

PROTEIN TERTIARY STRUCTURE More links form between the polypeptides (hydrogen and sulphide bonds) This forms fibrous proteins or globular proteins.

PROTEIN QUARTERNARY STRUCTURE Quarternary structure is formed when several polypeptides become bonded together

Protein structure Proteins fall into two distinct groups: Fibrous proteins Globular proteins

FIBROUS PROTEIN Formed when several polypeptide chains are bonded together in long parallel strands. Long rope-like structure e.g. collagen (skin) keratin (hair) actin and myosin (muscle)

Collagen Elastin Actin and myosin Keratin

GLOBULAR PROTEINS Look like a tangled ball of string. Several chains folded into a ball e.g. Enzymes Hormones Antibodies

Growth Hormone Prolactin

Glucagon Insulin

Active site

CONJUGATED PROTEIN Contains polypeptide chains and a non- protein part E.g. haemoglobin consists of 4 polypeptide chains and 4 iron atoms

Conjugated proteins

Proteins with an attached carbohydrate Glycoproteins Proteins with an attached carbohydrate e.g. Mucus.

Lipoproteins Proteins with an attached lipid. The products of fat digestion are coated with lipoprotein before being transported.

What is a mutation?

How do mutations occur? The Red Fox Ate The Pig The Fox Ate The Pig The Rd Fox Ate The Pig The Red Fox Ate The The Pig

Practical: At the end of your bench is a pot of sweets At random select 1 from the pot Round 1 Flu Epidemic Colour Mutation Red Able to fight off infection better Orange No mutation Yellow White Less able to fight off infection Green

Round 2 Intense sunshine and water shortage Colour Mutation Red No mutation Orange Prone to dehydration and sunstroke Yellow White Green Better able to store water and keep cool

Round 3 Heavy metal pollution Colour Mutation Red No mutation Orange Decreased tolerance to heavy metals Yellow White Increased tolerance to heavy metals Green

Round 4 Ebola epidemic Colour Mutation Red Ebola is always lethal Orange No mutation Yellow White Green Increased tolerance to ebola

Round 5 – Sickle cell anaemia Colour Mutation Red Sickle cell anaemia Orange Normal red blood cells Yellow White Green

Mutations A mutation is a change to an individuals DNA. There are 2 different types of mutation: Gene mutation Chromosome mutation. Mutations are the only source of new variation.

They occur naturally and at random but are rare. The mutation rate varies between genes and species. Mutagenic agents can increase the frequency of mutation. Some are advantageous, neutral or lethal!

EXAMPLES Polydactyly – presence of extra finger or toes Liam Gallagher and Marilyn Monroe!!

LIAM’S EXTRA TOE!

Gene Mutations Changes in one or more nucleotides in the DNA of the cell giving a change in the base sequence. 3 types of POINT MUTATION: SUBSTITUTION INSERTION DELETION Some mutation are small and the protein isn’t changed. Others results in different proteins or no protein at all.

Substitutions Change in one nucleotide in the DNA sequence of a single gene. This results in one or more codons for one or more amino acids being altered.

Substitution mRNA Protein Met Gln Thr Ser STOP mRNA Protein Met Gln

Substitution - Missense Mutation Change in the codon for an amino acid so that a different amino acid is inserted into the protein. An example of a disorder that results from a missense mutation is sickle cell anaemia. This may or may not have an effect on the final protein

Sickle Cell Anaemia

Substitution - Nonsense Mutations A codon for a specific amino acid being changed to a stop codon. It causes protein synthesis to stop early and results in a shorter protein which is unable to function. An example of this is Duchenne Muscular Distrophy

Splice-Site Mutations This is where a mutation happens at a site where an intron is being spliced – the intron does not get spliced. May cause non-functioning proteins.

Splice-Site Mutations Intron Exon Normal splicing Abnormal splicing Normal functional haeomoglobin with 4 oxygen carrying subunits Haeomoglobin with only 2 oxygen carrying subunits Thalassemia, a disease caused by a defect in haemoglobin synthesis, is caused by a splice site mutation.

Nucleotide repeats Where sections of the code are repeated (usually large copies of code are inserted. Gives extra copies of an amino acid or if too many repeats then the gene is silenced. Proteins are not always expressed but will be defective if they are. Example – Huntington’s

Frameshift Mutations Where the entire code is shifted affecting all amino acid codes after the point of mutation – large changes to the code Protein formed will be non-functioning Frameshift mutations can be: Insertion Deletion Tay-sachs and cystic fibrosis

Frameshift - insertion A nucleotide is added to the strand

Insertion mRNA Protein Met Gln Thr Ser STOP mRNA Protein Met Ala Asp Ile Leu

Frameshift - deletion A nucleotide is removed from the strand

Deletion mRNA Protein Met Gln Thr Ser STOP mRNA Protein Met Gln His Leu

Summary table Mutation Effect on the Protein Missense Nonsense Depends on the proteins role Nonsense Shorter protein that won’t function Splice - site Non-functioning protein Nucleotide Repeats Defective if expressed Frameshift Non- functioning protein

Research Task – 300 words Create a fact sheet to show some information that you have gathered on one of the following : Sickle – cell Thalassemia PKU DMD Tay – sachs Cystic fibrosis Huntington’s Fragile – X Your fact sheet should contain info about the effects the condition has on the body and the type of mutation that causes it.

Chromosome Mutations Chromosome structure mutations involve a change in the sequence or number of genes on a chromosome. It is lethal Examples are: Deletion Duplication Translocation

Deletion The chromosome breaks in 2 places and the segment in-between becomes detached. The 2 ends then join up giving a shorter chromosome which lacks certain genes. Drastic effect – e.g cri-du-chat

Duplication When a segment of its homologous partner becomes attached at one end, or inserted somewhere along its length. This results in a section of genes being repeated. Common cause of cancer

Translocation A section of one chromosome breaks off and becoming attached to another chromosome which is not its homologous partner. This usually leads to problems during pairing up in meiosis and the gametes formed are often non-viable. Common cause of cancer

Non-reciprocal translocation

Reciprocal translocation

Sickle Cell Videos Thalasessemia DMD Videos http://www.nhs.uk/video/pages/sickle-cell- anaemia.aspx?searchtype=Tag&searchterm=Conditions__Blood+diso rders& https://www.youtube.com/watch?v=2CsgXHdWqVs DMD Videos https://www.youtube.com/watch?v=6wuTEFRhh-I Documentary https://www.youtube.com/watch?v=L-5YkWqwVEg Thalasessemia https://www.youtube.com/watch?v=5GDvfQL03a8

Learning Intentions Describe the different structures of proteins Describe different functions of proteins To discuss the effects of mutations in the code

ESSAY TITLE Give an account of the replication of DNA ESSAY TITLE Give an account of the replication of DNA. (maximum of 7 marks)

ANSWERS DNA is unwound and unzipped… …by the enzyme helicase… …to form two template strands. DNA polymerase is the enzyme which adds nucleotides to the new DNA strand. DNA polymerase needs a primer to start replication. DNA polymerase can only add complementary nucleotides to the deoxyribose / 3  end of the DNA strand. This results in one strand / the leading strand being continuously replicated, and the other strand / the lagging strand being replicated in fragments, which are joined together (by the enzyme ligase).

ESSAY TITLE Give an account of gene expression under the following headings : Transcription (6 marks) Post-translational modification (PTM) (4 marks)

ANSWERS Transcription (maximum of 6 marks): Transcription is the formation of a mRNA molecule on a DNA template. DNA unwinds, and strands separate by the action of helicase. RNA nucleotides attach to exposed bases of DNA. DNA A pairs with RNA U, DNA T - RNA A, DNA G - RNA C and DNAC - RNA G. RNA polymerase joins nucleotides (to each other). This produces the primary transcript. Which contains introns and exons. Exons are protein coding sections of mRNA and introns are non-coding sections. Post-translational modification (PTM) (maximum of 4 marks): It takes place after the polypeptide has been completed on the ribosome. It allows several proteins to be formed from one gene. It may involve enzyme cutting and combining of polypeptide chains. e.g. insulin from pro-insulin. It may involve adding of phosphate or carbohydrate groups. Addition of phosphate enables enzymes / receptors to be switched 'on' and 'off'.