Biology 107 Macromolecules III

1. Biology 107Macromolecules III September 7, 2005

2. Proteins May Be Denatured and Renatured. When proteins are changed from one environment to another they usually change shape (denature). Return to the original environment commonly results in folding that is different than normally found under that condition.

3. Protein “Partners” (Chaperones) Influence Folding

4. Protein Chaperones Influence “Correct” Folding

5. Macromolecules III Student Objectives: As a result of this lecture and the assigned reading, you should understand the following: 1. Nucleic Acids are polymers of nucleotides. There are two types of nucleic acids: deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). 2. Nucleic acids function in information coding, storage and transfer. DNA does not directly control protein synthesis, instead it works through intermediates, RNA molecules.

6. Macromolecules III • Each nucleotide monomer has three (3) parts: five carbon sugar phosphate group nitrogenous base Nucleic acids contain one of two 5-carbon sugars, either deoxyribose (in DNA) or ribose (in RNA). Linked to the one end of the sugar is a phosphate group, and linked to the other end of the pentose is one of the nitrogenous bases. DNA has the nitrogenous bases adenine (A), guanine (G), thymine (T), and cytosine (C). RNA has A, G, C and uracil (U) (instead of thymine).

7. Macromolecules III • A nucleic acid polymer, a polynucleotide, forms from monomers covalently linked by dehydration synthesis. The phosphate group of one nucleotide bonds to the sugar of the next nucleotide, with the result a repeating sugar-phosphate backbone. • RNA is normally a single polynucleotide strand, while DNA is a double-stranded molecule. • Nucleic acids form complementary base pairs stabilized by hydrogen bonds, with guanine pairing with cytosine and adenine pairing with thymine or uracil.

8. Functions of Nucleic Acids Information coding, storage, and transfer Synthesis of other nucleic acids or proteins Central Dogma DNA ↓ RNA ↓ Protein

9. The Flow of Genetic Information (The Central Dogma)

10. We store lots of information using simple linear codes Mass Storage of Information

11. CTGGGTTCTGTTCGGGATCCCAGTCACAGGGACAATGGCGCATTCATATGTCACTTCCTTTACCTGCCTGGAGGAGGTGTGGCCACAGACTCTGGTGGCTGCGAACGGGGACTCTGACCCAGTCGACTTTATCGCCTTGACGAAGGGTTGGTTAATCCGTGCATGTGAGCTCCTCAGGGTGGAATCCAGGAGGATCCACGAGGGTGAATTGGCGGCATTCTTGTCTTACGCCATCGCCTACCCCCAAAACTTCCTGTCTGTGATTGACAGCTACAGCGTAGGATGCGGTCTGTTGAACTTCTGCGCGGTGGCTCTGGCTCTCTGTGAACTGGGCTACAGGCCTGTGGGGGTGCGTTTGGACAGCGGTGACCTCTGCAGCCTGTCGGTGGATGTCCGCCAGGTCTTCAGACGCTGCAGCGAGCATTTCTCCGTCCCTGCCTTTGATTCGTTGATCATCGTCGGGACGAATAACATCTCAGAGAAAAGCTTGACGGAGCTCAGCCTGAAGGAGAACCAGATTGACGTTGTCGGAGTCGGAACTCACCTGGTCACCTGTACGACTCAGCCGTCGCTGGGTTGCGTTTACAAGCTGGTGGAGGTGAGGGGGAGGCCCCGGATGAAGATCAGCGAGGATCCGGAAAAGAGCACCGTTCCCGGGAGGAAGCAGGTGTACCGCCTGATGGACACTGATGCTCCTCCAGAACCTGGAGTCCCTCTGAGCTGCTTCCCTCTGTGCTCCGATCGCTCCTCCGTCTCCGTCACCCCGGCGCAGGTTCACCGTCTGCGGCAGGAAGTCTTTGTTGATGGACAGGTCACAGCCCGTCTGTGCAGCGCCACAGAGACCAGAACGGAGGTCCAGACCGCTCTCAAGACCCTCCACCCTCGACACCAGAGGCTGCAGGAGCCAGACTCGTACACGGTGATTCACATTCTGAAGAAAACAACATTGGATCGCGCTTTTCCGCTCTCTTCCCTTAGTTTCCCCTCCGAACTCCGCCGCTGGGCCGGAGGACTGAACCGGCCCCCGACGGTGTCCCAGCGGCGGTGCAATGTGGCCCGGGTCCGGGAGGAGTGCGTGACGCCAGAGCAGAATGGTTCGGTGGACGGGGGCGCACACGCTTCTCGCCGCGGCCGCTCCCCGCGGCCCACGGAACCGCGGGATCGGAGCTGTTTTGTGCCGCCTGAAGGACTCGAAGGGGGACGGATAAATGCTGGATCCCCGAGTCCAGATCTGACCGTCTGCATTCCGCTGGTGAGCTGCCAGACGCATCTGGAAACGAGCGCCGACAGAAGCAGCTCCGGACCATGTCGCCGTCCGCGCACACAGGTCGCGTGTAAAGGGGACTTGGTCAGATCATCTTGCACCGGAACCAGGTCTCCCCTGGAGATGGGGACGGTCATGACCGTCTTCTACCAGAAGAAGTCCCAGCGGCCGGAGAGGAGAACCTTCCAGATCAAGCCTGACACGCGGCTCCTCGTGTGGAGCCGAAACCCCGACAAAAGCGAAGGAGAGAGTGAGTATGAGCAGGCGGGCCGTGCCGGGACCGGGCCCACGCCGCCCAGAACCTCATGTTCCTGGTGTTCCAGCACCGACCGGCCAGTTCTGGCTCAGCTCCACACAACATCTGACAAACCCTCGTGGTTCCTGGTGGTCGACCACACGGCTGGTGAGGCGGCCTCAGGTAGCTCAGGTAGCTCAGGTTAGCGTAAAGGGAGTTTTAAGCATCACCTGGTGACGGGGCAGGTGAGCTCCAGCCACTCAGCAGTGCACGGCCGTGCACATACACACACACCTCTGTGTCGAGGTTACAGGTGGGGCCAAAGCCCAACACCTTCAATGGCCCTCAGAGCTTTGAGGTTTTGAGGAATTGAGCCTTTAATCAGAAAACTGGGTTCTGTTCGGGATCCCAGTCACAGGGACAATGGCGCATTCATATGTCACTTCCTTTACCTGCCTGGAGGAGGTGTGGCCACAGACTCTGGTGGCTGCGAACGGGGACTCTGACCCAGTCGACTTTATCGCCTTGACGAAGGGTTGGTTAATCCGTGCATGTGAGCTCCTCAGGGTGGAATCCAGGAGGATCCACGAGGGTGAATTGGCGGCATTCTTGTCTTACGCCATCGCCTACCCCCAAAACTTCCTGTCTGTGATTGACAGCTACAGCGTAGGATGCGGTCTGTTGAACTTCTGCGCGGTGGCTCTGGCTCTCTGTGAACTGGGCTACAGGCCTGTGGGGGTGCGTTTGGACAGCGGTGACCTCTGCAGCCTGTCGGTGGATGTCCGCCAGGTCTTCAGACGCTGCAGCGAGCATTTCTCCGTCCCTGCCTTTGATTCGTTGATCATCGTCGGGACGAATAACATCTCAGAGAAAAGCTTGACGGAGCTCAGCCTGAAGGAGAACCAGATTGACGTTGTCGGAGTCGGAACTCACCTGGTCACCTGTACGACTCAGCCGTCGCTGGGTTGCGTTTACAAGCTGGTGGAGGTGAGGGGGAGGCCCCGGATGAAGATCAGCGAGGATCCGGAAAAGAGCACCGTTCCCGGGAGGAAGCAGGTGTACCGCCTGATGGACACTGATGCTCCTCCAGAACCTGGAGTCCCTCTGAGCTGCTTCCCTCTGTGCTCCGATCGCTCCTCCGTCTCCGTCACCCCGGCGCAGGTTCACCGTCTGCGGCAGGAAGTCTTTGTTGATGGACAGGTCACAGCCCGTCTGTGCAGCGCCACAGAGACCAGAACGGAGGTCCAGACCGCTCTCAAGACCCTCCACCCTCGACACCAGAGGCTGCAGGAGCCAGACTCGTACACGGTGATTCACATTCTGAAGAAAACAACATTGGATCGCGCTTTTCCGCTCTCTTCCCTTAGTTTCCCCTCCGAACTCCGCCGCTGGGCCGGAGGACTGAACCGGCCCCCGACGGTGTCCCAGCGGCGGTGCAATGTGGCCCGGGTCCGGGAGGAGTGCGTGACGCCAGAGCAGAATGGTTCGGTGGACGGGGGCGCACACGCTTCTCGCCGCGGCCGCTCCCCGCGGCCCACGGAACCGCGGGATCGGAGCTGTTTTGTGCCGCCTGAAGGACTCGAAGGGGGACGGATAAATGCTGGATCCCCGAGTCCAGATCTGACCGTCTGCATTCCGCTGGTGAGCTGCCAGACGCATCTGGAAACGAGCGCCGACAGAAGCAGCTCCGGACCATGTCGCCGTCCGCGCACACAGGTCGCGTGTAAAGGGGACTTGGTCAGATCATCTTGCACCGGAACCAGGTCTCCCCTGGAGATGGGGACGGTCATGACCGTCTTCTACCAGAAGAAGTCCCAGCGGCCGGAGAGGAGAACCTTCCAGATCAAGCCTGACACGCGGCTCCTCGTGTGGAGCCGAAACCCCGACAAAAGCGAAGGAGAGAGTGAGTATGAGCAGGCGGGCCGTGCCGGGACCGGGCCCACGCCGCCCAGAACCTCATGTTCCTGGTGTTCCAGCACCGACCGGCCAGTTCTGGCTCAGCTCCACACAACATCTGACAAACCCTCGTGGTTCCTGGTGGTCGACCACACGGCTGGTGAGGCGGCCTCAGGTAGCTCAGGTAGCTCAGGTTAGCGTAAAGGGAGTTTTAAGCATCACCTGGTGACGGGGCAGGTGAGCTCCAGCCACTCAGCAGTGCACGGCCGTGCACATACACACACACCTCTGTGTCGAGGTTACAGGTGGGGCCAAAGCCCAACACCTTCAATGGCCCTCAGAGCTTTGAGGTTTTGAGGAATTGAGCCTTTAATCAGAAAA Mass Storage of Information Another simple linear code, the DNA sequence, is the basis of life

12. Dense Information Storage This image shows 1 gram of DNA on a CD that can hold 800 MB of data. The 1 gram of DNA can hold about 1x1014 MB of data. The number of CDs required to hold this amount of information, lined up edge to edge, would circle the Earth 375 times, and would take 163,000 centuries to listen to.

13. DNA as Mass Storage Device If the DNA sequence from a single human sperm cell were typed on a continuous ribbon in ten-pitch type, that ribbon could be stretched from San Francisco to Chicago to Washington to Houston to Los Angeles, and back to San Francisco, with about 60 miles of ribbon left over.

14. Structure of Nucleotides

15. Structure of Nucleotides Pentose sugar Phosphate group Nitrogenous base

16. Nitrogenous Bases

17. Chargaff’s Rules Erwin Chargaff’s data indicated that in DNA the amount of adenine nearly always equaled the amount of thymine and the amount of cytosine nearly always equaled the amount of guanine.

18. Double Helix Structure of DNA 1953 2003 Original Nature paper by Watson and Crick – 1953 Click to Open

19. Thread of History

20. Thread of History

21. The Eagle

22. Questions to Consider For Watson and Crick Paper • What was one of the reasons Watson and Crick did not expect the phosphate groups in DNA to be aligned along the axis of the DNA molecule? • What is the means by which the individual strands in DNA are joined together? • What is the consequence of knowing the base sequence of one strand? What is the implication for copying the genetic material?

23. DNA Is Normally Double-Stranded Each strand has polarity (5’ and 3’ ends). In double-stranded DNA each strand is oriented “anti-parallel” to the other strand. The strands are normally held together by hydrogen bonds. The optimal hydrogen bonding is when A bonds with T and G bonds with C.

24. Base Pairing in DNA G/C pairs have three hydrogen bonds A/T pairs have two hydrogen bonds

25. Double Helix

26. Nucleic Acid Gel Electrophoresis

27. The Sequence of Nucleotides Encodes Information _ +

28. The Double Helix Structure of Complementary Strands Explains The Mechanism of DNA Replication

29. ATP Is a Nucleotide

30. ATP Structure and Hydrolysis

31. Summary of Adenine Phosphates 1. ATP (adenosine triphosphate) = 3 phosphate groups + adenine + ribose sugar a. This is the high energy form b. The energy is greatest in the bond holding the third phosphate - that bond is easily broken. 2. ADP (adenosine diphosphate) = 2 phosphate groups + adenine + ribose sugar a. This is the low energy form b. ADP can be recharged into ATP by addition of phosphate, if a phosphate source and enough energy are available. 3. AMP (adenosine monophosphate) = 1 phosphate group + adenine + ribose sugar a. Intracellular activator of processes

32. Additional Resources http://www.nature.com/nature/dna50/ - Anniversary issue of Nature celebrating the 50th year following the original DNA structure articles. Interesting links. Article about Rosalind Franklin. http://www.genome.gov/10001772 - Federal Human Genome Project website. http://www.time.com/time/time100/scientist/profile/watsoncrick.html - short recount of Watson and Crick at Cambridge. http://www.dnai.org/index.htm - Home page for DNA Interactive. Time lines and interesting historical information. Photos at: http://www.dnai.org/album/6/album.html.