1. Proteins
Function and Structure

2. Proteins more than 50% of dry mass of most cells functions include
structural support
storage, transport
cellular communications
movement
defense against foreign substances (immunity)
- enzymatic reactions

4. Structure of Proteins Monomer: amino acid
20 different a.a. used in cells
Polymer of amino acids-->polypeptide
Complex of >1 polypeptides-->protein

5. Amino Acid Structure Organic molecules with Amino end ? Carboxyl end ?
Central -carbon
Distinct side chain (or R group) bonded to -carbon

6. What happens to ends in a cellular environment?
LE 5-UN78
a carbon
What happens to ends in a cellular environment?
Amino
group
Carboxyl
group

7. Amino acids Memorize structure LE 5-17a Glycine (Gly) Alanine (Ala)
Valine (Val)
Leucine (Leu)
Isoleucine (Ile)
Nonpolar
Methionine (Met)
Phenylalanine (Phe)
Tryptophan (Trp)
Proline (Pro)

8. LE 5-17b Polar Serine (Ser) Threonine (Thr) Cysteine (Cys)
Tyrosine (Tyr)
Asparagine (Asn)
Glutamine (Gln)

9. LE 5-17c
Acidic
Basic
Electrically
charged
Aspartic acid (Asp)
Glutamic acid (Glu)
Lysine (Lys)
Arginine (Arg)
Histidine (His)

10. Polypeptides range in length
Amino acids
linked together through peptide bonds
Draw dipeptide bond showing bond
Polypeptides range in length
a few a.a. to > thousand
Each polypeptide has unique linear sequence of amino acids

11. Protein Conformation
Helices, coils, pleats
Sequence of amino acids determines 3-D conformation--> function
Depicted in ribbon and space-filling models

12. LE 5-19
Groove
A ribbon model
Groove
A space-filling model

13. Four Levels of Protein Structure
Primary structure (1o)
unique sequence of amino acids, like letters in a word
Secondary structure (2o)
-helices and -pleated sheets
Stabilized by H-bonds
Tertiary structure (3o)
determined by interactions among various side chains
(R groups)
Quaternary structure (4o)
Multiple polypeptide chains forming a functional protein

14. LE 5-20a
1o structure
Amino end
Amino acid
subunits
Carboxyl end

15. Four Levels of Protein Structure
Primary structure (1o)
unique sequence of amino acids, like letters in a word
Secondary structure (2o)
-helices and -pleated sheets
Stabilized by H-bonds between amino and carbonyl groups
- Creates 3-D conformation
Tertiary structure (3o)
determined by interactions among various side chains
(R groups)
Quaternary structure (4o)
Multiple polypeptide chains forming a functional protein

16. LE 5-20b
2o structure
b pleated sheet
Amino acid
subunits
 helix

17. Four Levels of Protein Structure
Primary structure (1o)
unique sequence of amino acids, like letters in a word
Secondary structure (2o)
-helices and -pleated sheets
Stabilized by H-bonds
Tertiary structure (3o)
- determined by bonds between side chains
(R groups) often between linearly distant amino acids
-ionic bonds, disulfide bonds, van der Waals forces, H-bonds
- creates to 3-D conformation
Quaternary structure (4o)
Multiple polypeptide chains forming a functional protein

18. LE 5-20d
Hydrophobic
interactions and
van der Waals
interactions
Polypeptide
backbone
Hydrogen
bond
Disulfide bridge
Ionic bond

19. Four Levels of Protein Structure
Primary structure (1o)
unique sequence of amino acids, like letters in a word
Secondary structure (2o)
-helices and -pleated sheets
Stabilized by H-bonds
Tertiary structure (3o)
- determined by bonds between side chains
(R groups) often between linearly distant amino acids
-ionic bonds, disulfide bonds, van der Waals forces, H-bonds
- contributes to 3-D conformation
Quaternary structure (4o)
Multiple polypeptide chains forming a functional protein

20. Polypeptide chain b Chains Iron Heme a Chains Hemoglobin
LE 5-20e
Polypeptide
chain
b Chains
Iron
Heme
a Chains
Hemoglobin
Polypeptide chain
Collagen

21. LE 5-20
b pleated sheet
+H3N
Amino end
Amino acid
subunits
 helix

22. Significance of Protein Conformation
Small change in 1o structure
can change protein’s conformation and function
Example
Sickle-cell disease
an inherited blood disorder-->anemia
Caused by single amino acid substitution in hemoglobin

23. Sickled RBC Normal RBC Normal cells are full of individual hemoglobin
LE 5-21a
Normal cells are
full of individual
hemoglobin
molecules, each
carrying oxygen.
10 µm
Fibers of abnormal
hemoglobin deform
cell into sickle
shape.
Normal RBC
Sickled RBC

24. One Amino Acid Substitution: Huge Effect!
LE 5-21b
One Amino Acid Substitution: Huge Effect!
Normal hemoglobin
Sickle-cell hemoglobin
Primary
structure
Val
His
Leu
Thr
Pro
Glu
Glu
Primary
structure
Val
His
Leu
Thr
Pro
Val
Glu 1 2 3 4 5 6 7 1 2 3 4 5 6 7
Exposed
hydrophobic
region
Secondary
and tertiary
structures
Secondary
and tertiary
structures
b subunit
b subunit a a  
Quaternary
structure
Normal
hemoglobin
(top view)
Quaternary
structure
Sickle-cell
hemoglobin a   a
Function
Molecules do
not associate
with one
another; each
carries oxygen.
Function
Molecules
interact with
one another to
crystallize into
a fiber; capacity
to carry oxygen
is greatly reduced.

25. ? Environment Affects Protein Structure & Function pH
salt concentration
temperature
other environmental factors
Extreme conditions cause
unraveling of protein structure:denaturation

26. Caused by, for example, high temperature (100oC)
Denaturation
Normal protein
Denatured protein
Renaturation
Lowered Temp (37oC)

27. Proper Protein-Folding
Chaperonins
protein complexes that assist in the proper folding of other proteins

28. Chaperonin (fully assembled)
LE 5-23a
Cap
Hollow
cylinder
Chaperonin
(fully assembled)

29. Model Correctly folded protein Polypeptide Steps of Chaperonin Action:
LE 5-23b
Model
Correctly
folded
protein
Polypeptide
Steps of Chaperonin
Action:
The cap attaches, causing
the cylinder to change
shape in such a way that
it creates a hydrophilic
environment for the
folding of the polypeptide.
The cap comes
off, and the
properly folded
protein is released.
An unfolded poly-
peptide enters the
cylinder from one
end.

30. Techniques to Determine Protein Structure
X-ray crystallography (need to make protein crystals)
Nuclear magnetic resonance (NMR) spectroscopy (not dependent on making protein crystals)

31. How is the sequence of proteins determined?
-encoded in DNA
- two step process to decode
DNA is transcribed into mRNA
2. mRNA is translated into polypetide
More later