1. Molecules of Life
Chapter 3 Part 2

2. 3.5 Proteins – Diversity in Structure and Function
Proteins are the most diverse biological molecule (structural, nutritious, enzyme, transport, communication, and defense proteins)
Cells build thousands of different proteins by stringing together amino acids in different orders

3. Proteins and Amino Acids
An organic compound composed of one or more chains of amino acids
Amino acid
A small organic compound with an amine group (—NH3+), a carboxyl group (—COO-, the acid), and one or more variable groups (R group)

4. Amino Acid Structure

5. amine group carboxyl group valine
Figure 3.15
Generalized structure of amino acids, and an example. Green boxes highlight R groups. Appendix V has models of all twenty of the common amino acids.
valine
Fig. 3-15, p. 44

6. COMMON AMINO ACIDS
20 common amino acids make up the multitude of proteins we know of

7. Amino Acids With Aliphatic Side Chains

8. Amino Acids With Aliphatic Side Chains

9. Amino Acids With Aliphatic Side Chains

10. Amino Acids With Aromatic Side Chains

11. Amino Acids With Hydroxyl Side Chains

12. Amino Acid with a Sulfhydryl Side Chain

13. Disulfide Bond Formation

14. Amino Acids With Basic Side Chains

15. Amino Acids With Acidic Side Chains and Their Amide Derivatives

17. There are some important uncommon amino acids

18. Polypeptides
Protein synthesis involves the formation of amino acid chains called polypeptides
Polypeptide
A chain of amino acids bonded together by peptide bonds in a condensation reaction between the amine group of one amino acid and the carboxyl group of another amino acid

19. Peptide Bond Formation

20. Figure 3.16
Examples of peptide bond formation. Chapter 14 returns to protein synthesis.
Fig. 3-16a, p. 44

21. Figure 3.16
Examples of peptide bond formation. Chapter 14 returns to protein synthesis.
A DNA encodes the
order of amino acids in a new polypeptide chain. Methionine (met) is typically the first amino acid.
B In a condensation reaction, a peptide bond forms between the methionine and the next amino acid, alanine (ala) in this example. Leucine (leu) will be next. Think about polarity, charge, and other properties of functional groups that become neighbors in the growing chain.
Fig. 3-16a, p. 44

22. Figure 3.16
Examples of peptide bond formation. Chapter 14 returns to protein synthesis.
Fig. 3-16b, p. 45

23. will be next. The chain is starting to
C A peptide bond forms between the alanine and leucine. Tryptophan (trp)
will be next. The chain is starting to
twist and fold as atoms swivel around some bonds and attract or repel their neighbors.
D The sequence of amino acid subunits in this newly forming peptide chain is now met–ala–leu–trp. The process may continue until there are hundreds or thousands of amino acids in the chain.
Figure 3.16
Examples of peptide bond formation. Chapter 14 returns to protein synthesis.
Fig. 3-16b, p. 45

24. A DNA encodes the
order of amino acids in a new polypeptide chain. Methionine (met) is typically the first amino acid.
B In a condensation reaction, a peptide bond forms between the methionine and the next amino acid, alanine (ala) in this example.
Leucine (leu) will be next. Think about polarity, charge, and other properties of functional groups that become neighbors in the growing chain.
Figure 3.16
Examples of peptide bond formation. Chapter 14 returns to protein synthesis.
Stepped Art
Fig. 3-16a, p. 44

25. C A peptide bond forms between the alanine and leucine.
Tryptophan (trp) will be next. The chain is starting to twist and fold as atoms swivel around some bonds and attract or repel their neighbors.
C A peptide bond forms between the alanine and leucine.
D The sequence of amino acid subunits in this newly forming peptide chain is now met–ala–leu–trp. The process may continue until there are hundreds or thousands of amino acids in the chain.
Figure 3.16
Examples of peptide bond formation. Chapter 14 returns to protein synthesis.
Stepped Art
Fig. 3-16b, p. 45

26. Animation: Peptide bond formation

27. Levels of Protein Structure
Primary structure
The unique amino acid sequence of a protein
Secondary structure
The polypeptide chain folds and forms hydrogen bonds between amino acids

28. Levels of Protein Structure
Tertiary structure
A secondary structure is compacted into structurally stable units called domains
Forms a functional protein
Quaternary structure
Some proteins consist of two or more folded polypeptide chains in close association
Example: hemoglobin

29. Levels of Protein Structure

30. 3.6 Why Is Protein Structure So Important?
When a protein’s structure goes awry, so does its function

31. Figure 3.17
Four levels of a protein’s structural organization.
Fig. 3-17a, p. 45

32. a Protein primary structure: Amino acids bonded as a polypeptide chain.
Figure 3.17
Four levels of a protein’s structural organization.
Fig. 3-17a, p. 45

33. Figure 3.17
Four levels of a protein’s structural organization.
Fig. 3-17b, p. 45

34. b Protein secondary structure: A coiled (helical) or sheetlike array held in place by hydrogen bonds (dotted lines) between different parts of the polypeptide chain.
Figure 3.17
Four levels of a protein’s structural organization.
helix (coil)
sheet
Fig. 3-17b, p. 45

35. Secondary Structure
The regular local structure based on the hydrogen bonding pattern of the polypeptide backbone
α helices
β strands (β sheets)
Turns and Loops
WHY will there be localized folding and twisting? Are all conformations possible?

36. α Helix First proposed by Linus Pauling and Robert Corey in 1951.
3.6 residues per turn, 1.5 Angstroms rise per residue
Residues face outward

37. α Helix
α-helix is stabilized by H-bonding between CO and NH groups
Except for amino acid residues at the end of the α-helix, all main chain CO and NH are H-bonded

38. α Helix representation

40. β strand
Fully extended
β sheets are formed by linking 2 or more strands by H-bonding
Beta-sheet also proposed by Corey and Pauling in 1951.

42. PARALLEL
ANTIPARALLEL

43. The Beta Turn (aka beta bend, tight turn)
allows the peptide chain to reverse direction
carbonyl C of one residue is H-bonded to the amide proton of a residue three residues away
proline and glycine are prevalent in beta turns

44. Mixed β Sheets

45. Twisted β Sheets

47.  Loops

48. What Determines the Secondary Structure?
The amino acid sequence determines the secondary structure
The α helix can be regarded as the default conformation
– Amino acids that favor α helices:
Glu, Gln, Met, Ala, Leu
– Amino acids that disrupt α helices:
Val, Thr, Ile, Ser, Asx, Pro

50. Figure 3.17
Four levels of a protein’s structural organization.
Fig. 3-17c, p. 45

51. c Protein tertiary structure: A chain’s coils, sheets, or both fold and twist into stable, functional domains such as barrels or pockets.
barrel
Figure 3.17
Four levels of a protein’s structural organization.
Fig. 3-17c, p. 45

52. Tertiary Structure The overall 3-D fold of a single polypeptide chain
The amino acid sequence determines the tertiary structure (Christian Anfinsen)
The polypeptide chain folds so that its hydrophobic side chains are buried and its polar charged chains are on the surface
Exception : membrane proteins
Reverse : hydrophobic out, hydrophilic in
Driven by hydrophobic interactions
Stabilized by H-bonding, LDF, noncovalent interactions, dipole interactions, ionic interactions, disulfide bonds

53. Fibrous and Globular Proteins

54. Fibrous Proteins
Much or most of the polypeptide chain is organized approximately parallel to a single axis
Fibrous proteins are often mechanically strong
Fibrous proteins are usually insoluble
Usually play a structural role in nature

55. Examples of Fibrous Proteins
Alpha Keratin: hair, nails, claws, horns, beaks
Beta Keratin: silk fibers (alternating Gly-Ala-Ser)

56. Examples of Fibrous Proteins
Collagen: connective tissue- tendons, cartilage, bones, teeth
Nearly one residue out of three is Gly
Proline content is unusually high
Unusual amino acids found: (4-hydroxyproline, 3-hydroxyproline , 5-hydroxylysine)
Special uncommon triple helix!

57. Globular Proteins
Most polar residues face the outside of the protein and interact with solvent
Most hydrophobic residues face the interior of the protein and interact with each other
Packing of residues is close but empty spaces exist in the form of small cavities
Helices and sheets often pack in layers
Hydrophobic residues are sandwiched between the layers
Outside layers are covered with mostly polar residues that interact favorably with solvent

58. An amphiphilic helix in flavodoxin:
A nonpolar helix in citrate synthase:
A polar helix in calmodulin:

60. Figure 3.17
Four levels of a protein’s structural organization.
Fig. 3-17d, p. 45

61. d Protein quaternary structure: two or more polypeptide chains associated as one molecule.
Figure 3.17
Four levels of a protein’s structural organization.
Fig. 3-17d, p. 45

62. Quaternary Structures
Spatial arrangement of subunits and the nature of their interactions. Can be hetero and/or homosubunits
Simplest example: dimer (e.g. insulin)
ADVANTAGES of 4o Structures
Stability: reduction of surface to volume ratio
Genetic economy and efficiency
Bringing catalytic sites together
Cooperativity

64. Protein Folding CHAPERONES assist protein folding
The largest favorable contribution to folding is the entropy term for the interaction of nonpolar residues with the solvent
CHAPERONES assist protein folding
to protect nascent proteins from the concentrated protein matrix in the cell and perhaps to accelerate slow steps

65. helix (coil) sheet barrel
a) Protein primary structure: Amino acids bonded as a polypeptide chain.
helix (coil)
sheet
b) Protein secondary structure: A coiled (helical) or sheetlike array held in place by hydrogen bonds (dotted lines) between different parts of the polypeptide chain.
barrel
c) Protein tertiary structure: A chain’s coils, sheets, or both fold and twist into stable, functional domains such as barrels or pockets.
Figure 3.17
Four levels of a protein’s structural organization.
d) Protein quaternary structure: two or more polypeptide chains associated as one molecule.
Stepped Art
Fig. 3-17, p. 45

66. Just One Wrong Amino Acid…
Hemoglobin contains four globin chains, each with an iron-containing heme group that binds oxygen and carries it to body cells
In sickle cell anemia, a DNA mutation changes a single amino acid in a beta chain, which changes the shape of the hemoglobin molecule, causing it to clump and deform red blood cells

67. Globin Chains in Hemoglobin

68. Figure 3.18
Globin and hemoglobin. (a) Globin, a coiled polypeptide chain that cradles heme, a functional group with an iron atom. (b) Hemoglobin, an oxygen-transport protein in red blood cells.
Fig. 3-18a, p. 46

69. alpha globin
heme
A Globin. The secondary structure of this protein includes several helices. The coils fold up to form a pocket that cradles heme, a functional group with an iron atom at its center.
Figure 3.18
Globin and hemoglobin. (a) Globin, a coiled polypeptide chain that cradles heme, a functional group with an iron atom. (b) Hemoglobin, an oxygen-transport protein in red blood cells.
Fig. 3-18a, p. 46

70. Figure 3.18
Globin and hemoglobin. (a) Globin, a coiled polypeptide chain that cradles heme, a functional group with an iron atom. (b) Hemoglobin, an oxygen-transport protein in red blood cells.
Fig. 3-18b, p. 46

71. alpha globin alpha globin beta globin beta globin
Figure 3.18
Globin and hemoglobin. (a) Globin, a coiled polypeptide chain that cradles heme, a functional group with an iron atom. (b) Hemoglobin, an oxygen-transport protein in red blood cells.
beta globin
beta globin
B Hemoglobin is one of the proteins with quaternary structure. It consists of four globin molecules held together by hydrogen bonds. To help you distinguish among them, the two alpha globin chains are shown here in green, and the two beta globin chains are in brown.
Fig. 3-18b, p. 46

72. Animation: Globin and hemoglobin structure

73. Molecular Basis of Sickle Cell Anemia

74. Figure 3.19
Sickle-cell anemia’s molecular basis and symptoms. Section 18.6 explores evolutionary and ecological pressures that maintain this genetic disorder in human populations.
Fig. 3-19a, p. 47

75. glutamic acid glutamic acid
valine
histidine
leucine
threonine
proline
Figure 3.19
Sickle-cell anemia’s molecular basis and symptoms. Section 18.6 explores evolutionary and ecological pressures that maintain this genetic disorder in human populations.
A Normal amino acid sequence at the start of the hemoglobin beta chain.
Fig. 3-19a, p. 47

76. Figure 3.19
Sickle-cell anemia’s molecular basis and symptoms. Section 18.6 explores evolutionary and ecological pressures that maintain this genetic disorder in human populations.
Fig. 3-19b, p. 47

77. valine histidine leucine threonine proline valine glutamic acid
Figure 3.19
Sickle-cell anemia’s molecular basis and symptoms. Section 18.6 explores evolutionary and ecological pressures that maintain this genetic disorder in human populations.
B One amino acid substitution results in the abnormal beta chain of HbS molecules. The sixth amino acid in such chains is valine, not glutamic acid.
Fig. 3-19b, p. 47

78. Figure 3.19
Sickle-cell anemia’s molecular basis and symptoms. Section 18.6 explores evolutionary and ecological pressures that maintain this genetic disorder in human populations.
Fig. 3-19c, p. 47

79. is a farm tool that has a crescent-shaped blade.) sickled cell
C Glutamic acid carries a negative charge; valine carries no charge. This difference changes the protein so it behaves differently. At low oxygen levels, HbS molecules stick together and form rod-shaped clumps that distort normally rounded red blood cells into sickle shapes. (A sickle
is a farm tool that has a crescent-shaped blade.)
sickled cell
normal cell
Figure 3.19
Sickle-cell anemia’s molecular basis and symptoms. Section 18.6 explores evolutionary and ecological pressures that maintain this genetic disorder in human populations.
Fig. 3-19c, p. 47

80. Figure 3.19
Sickle-cell anemia’s molecular basis and symptoms. Section 18.6 explores evolutionary and ecological pressures that maintain this genetic disorder in human populations.
Fig. 3-19d, p. 47

81. Clumping of cells in bloodstream
Circulatory problems, damage to brain, lungs, heart, skeletal muscles, gut, and kidneys
Heart failure, paralysis, pneumonia, rheumatism, gut pain, kidney failure
Spleen concentrates sickle cells
Spleen enlargement
Immune system compromised
Rapid destruction of sickle cells
Figure 3.19
Sickle-cell anemia’s molecular basis and symptoms. Section 18.6 explores evolutionary and ecological pressures that maintain this genetic disorder in human populations.
Anemia, causing weakness, fatigue, impaired development, heart chamber dilation
Impaired brain function, heart failure
D Melba Moore is a celebrity spokesperson for sickle-cell anemia organizations. Right, range of symptoms for a person with two mutated genes for hemoglobin’s beta chain.
Fig. 3-19d, p. 47

82. Animation: Sickle-cell anemia

83. Proteins Undone – Denaturation
Proteins function only as long as they maintain their correct three-dimensional shape
Heat, changes in pH, salts, and detergents can disrupt the hydrogen bonds that maintain a protein’s shape
When a protein loses its shape and no longer functions, it is denatured

84. 3.5-3.6 Key Concepts: Proteins
Structurally and functionally, proteins are the most diverse molecules of life
They include enzymes, structural materials, and transporters
A protein’s function arises directly from its structure