Lesson Objectives 22015 Content Objective Recognize how protein

Lesson Objectives 2/20/15 • Content Objective: Recognize how protein structure affects function. • Language Objective: Explain the significance of the STOP codon.

Entry Task: Educated Guess! Given your understanding of Central Dogma, hypothesize what the purpose of a “stop” codon might be. Write your hypothesis in your lab notebook, and bonus points for a picture!

Cystic Fibrosis https: //www. youtube. com/watch? v=z 0 rxyd. Solw. U

Cystic Fibrosis • Affects 30, 000 Americans and about 70, 000 people worldwide. • In people with CF, a defective gene and its protein product cause the body to produce unusually thick, sticky mucus that: – Clogs the lungs and leads to life-threatening lung infections. – Obstructs the pancreas and stops natural enzymes from helping the body break down food and absorb vital nutrients.

Cystic Fibrosis Pathology

Cystic Fibrosis • In the 1950 s, few children with CF lived to attend elementary school. Since then, tremendous progress in understanding and treating CF has led to dramatic improvements in the length and quality of life for those with CF. Many people with the disease can now expect to live into their 30 s, 40 s and beyond. Source: Cystic Fibrosis Foundation website

Cystic Fibrosis Genetics • CF is caused by mutations in a gene that produces a protein, called CFTR. The CFTR protein controls the flow of salt and water in and out of the cells of organs like the lungs and pancreas. • To have cystic fibrosis, a person must inherit two copies of the defective CF gene — one copy from each parent. Both parents must have at least one copy of the defective gene.

The Cystic Fibrosis Transmembrane Conductance Receptor (CFTR) conducts chloride ions across epithelial cell membranes.

CFTR Mutations

Types of Genetic Mutations

There Are 3 “Stop” Codons

STOP! The Game 1. 2. 3. 4. Start with 5 randomly selected amino acids (AAs) Identify an RNA sequence encoding the AAs Convert the RNA sequence to DNA Mutate a single DNA base to introduce nonsense mutation (a STOP codon) 5. If no STOP is found, additional AAs 6. The first person to STOP the growing DNA sequence wins

HCIVV

HCIVV His – Cys – Ile – Val

HCIVV His – Cys – Ile – Val CAU – UGU – AUU – GUA CAU – UGA – AUU – GUA

AKAVY

AKAVY Ala – Lys – Ala – Val – Tyr

AKAVY Ala – Lys – Ala – Val – Tyr GCU – AAA – GCU – GUU – UAU GCU – AAA – GCU – GUU – UAA

FKQPF

FKQPF Phe – Lys – Gln – Pro – Phe

FKQPF Phe – Lys – Gln – Pro – Phe UUU – AAG – CAA – CCC – UUC UUU – UAG – CAA – CCC – UUC

LYWHG

LYWHG Lys – Tyr – Trp – His – Gly

LYWHG Lys – Tyr – Trp – His – Gly CUA – UAU – UGG – CAU – GGA CUA – UAA – UGG – CAU – GGA