Human Cells Genes and proteins in health and disease Higher Human Biology Human Cells Genes and proteins in health and disease

a. Protein structure and function What do you remember? Write down 10 words you associate with protein structure and function

What you need to know The elements that are found in proteins The bonds that build protein shape The variety and function of proteins

Protein structure The elements making proteins are C, H, O, N and often S Amino acids are joined with peptide bonds (polypeptides) Hydrogen bonds form between amino acids giving initial folding or coiling (sheets/helices) Sulfur bridges and other interactions between negative and positive charges More than 1 chain of amino acids can join together Non protein molecules can be associated with proteins 3 dimensional shape

Fibrous Globular

What type of protein? What type of protein are these? What do they do? Collagen Somatotrophin Ligament Mucus Tubulin Testosterone Trypsin Endorphins Immunoglobulin What type of protein are these? What do they do? How is their structure related to their function?

Types of protein Protein structure allows protein function Enzymes – globular . Folded proteins exposing active sites to binds specific substrate. Speed up biochemical reactions. Structural proteins – fibrous often globular but too. Cell membranes, muscle fibres Hormones – globular . Folded into specific shape to bind to receptors at specific sites. Regulate growth and metabolism Antibodies –globular Y shape . Bind to specific antigens Haemoglobin – conjugated. Protein with non protein molecule attached to transport oxygen

What do you know? Name the elements in proteins State the number of amino acids in human proteins Name the 3 types of bonds involved in protein structure Name the 3 broad groups of protein For each group of protein name an example For each protein example describe how its structure relates to its function Complete the questions from page 50 in the textbook

b. Mutations and their effect on protein function What do you remember? Write down 10 words you associate with mutations, proteins and their function

What you need to know Some types of gene mutations, what causes them and how they affect protein function Some types of chromosome mutations, what causes them and how they affect protein function or organism function

Mutations A change in an organisms genome Could be small with a single gene Could be larger change to chromosome structure or number Occur spontaneously, naturally, randomly, rarely Rate can be artificially increased by mutagenic agents e.g. UV light, X-rays, gamma rays, mustard gas etc. These mutations would be described as induced

Mutations and protein function Proteins are essential for life Proteins are structural and control the metabolism If a gene coding for a protein mutates, the amino acid sequence could be altered Faulty protein gives faulty structure or faulty metabolic pathway If a gene coding for a protein mutates, the protein may not be made at all Missing protein could mean non-functioning metabolic pathway

Gene mutations Mutations on a single gene would alter the nucleotide sequence Point mutations are the change in one nucleotide Could be deletion of one nucleotide changing all the following codons and hence amino acid sequence. Could be insertion of one nucleotide changing all the following codons and hence amino acid sequence. These two are both frameshift mutations Could be the substitution of one nucleotide for another altering only 1 codon and amino acid in the sequence

Gene mutations - Normal

Gene mutations - Deletion

Gene mutations - Insertion

Gene mutations - Substitution

Gene mutations Splice site mutations during processing of primary transcript mRNA the introns are removed. Exons join together by splicing to give coding for aa’s. Splicing is controlled by nucleotide sequences at splice sites on introns next to exons. If a mutation occurs at splice sites some introns may be left in and coded for in the mature mRNA

Gene mutations Splice site mutations

Gene mutations Nucleotide sequence repeat expansion A mutation that produces a repeat of a triplet of nucleotides (trinucleotide). This inserted repeat of the same triplet codon (often many times) stops the protein from functioning, due too many aa’s.

Gene mutations Nucleotide sequence repeat expansion

How do gene mutations change protein structure Substitutions alter only 1 codon so only 1 aa is affected When the code still makes sense but is different from original it is called a missense mutation. When the code causes the sequence to stop being read as the mutation produces a stop codon it is called a nonsense mutation. The polypeptide chain is shortened and the protein is not properly formed.

How do gene mutations change protein structure Splice site mutation (retaining introns) Modifying mRNA can give altered protein structure. Frameshift (seen in nucleotide insertions or deletions) These change all the codons after the change so all the amino acids change after it. The protein produced is likely to be non-functional

How do gene mutations change protein structure Nucleotide sequence repeat expansion This is producing multiple copies of the same codon. Can give extra amino acids of the same type. Can expand the sequence so much that protein fails to be produced. Most of the gene mutations produce genetic disorders that have adverse effects on the individuals who suffer from it.

Effects on Health Many gene mutations have an effect on the structure and function of proteins. These changes have an effect on health for e.g. Sickle cell disease (anaemia) missense PKU missense Duchenne muscular dystrophy nonsense Tay-Sachs syndrome frameshift insertion Cystic fibrosis frameshift deletion Beta thalessemia splice site mutation Fragile X syndrome nucleotide sequence repeat expansion Huntingdon’s disease nucleotide sequence repeat expansion

Chromosome mutations These affect the structure of a whole chromosome. These include: Deletion where part of a chromosome is lost Duplication where part of the chromosome is repeated Translocation where 2 or more chromosomes rearrange materials between them Because these are such large changes they are often lethal in their effect.

Chromosome deletion

Chromosome duplication

Chromosome translocation

What do you know now? What 2 effects can a mutation have on protein production? What are the 3 types of single gene mutation? What is a missense mutation? What is a nonsense mutation? What is a splice site mutation What 2 types of nucleotide changes are frameshift mutations? What is a nucleotide sequence repeat mutation? What are the 3 chromosome mutations? What happens in each of these mutations?

Consolidation Reading PPT, textbook or scholar and making own notes. Completing textbook questions page 50 and p62 Answer multiple choice questions chapter 4