Transcript Proteins : Structure & Function

Proteins
Function and Structure
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
Structure of Proteins
• Monomer: amino acid
• 20 different a.a. used in cells
• Polymer of amino acids-->polypeptide
Complex of >1 polypeptides-->protein
Amino Acid Structure
• Organic molecules with
– Amino end
?
– Carboxyl end
?
– Central -carbon
– Distinct side chain (or R group) bonded to -carbon
LE 5-UN78
 carbon
What happens to ends in a cellular environment?
Amino
group
Carboxyl
group
LE 5-17a
Amino acids
Memorize structure
Glycine (Gly)
Alanine (Ala)
Valine (Val)
Leucine (Leu)
Isoleucine (Ile)
Nonpolar
Methionine (Met)
Phenylalanine (Phe)
Tryptophan (Trp)
Proline (Pro)
LE 5-17b
Polar
Serine (Ser)
Threonine (Thr)
Cysteine (Cys)
Tyrosine (Tyr)
Asparagine (Asn) Glutamine (Gln)
LE 5-17c
Acidic
Basic
Electrically
charged
Aspartic acid (Asp) Glutamic acid (Glu)
Lysine (Lys)
Arginine (Arg)
Histidine (His)
• 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
Protein Conformation
• Helices, coils, pleats
• Sequence of amino acids determines 3-D
conformation--> function
• Depicted in ribbon and space-filling models
LE 5-19
Groove
A ribbon model
Groove
A space-filling model
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
LE 5-20a
1o
structure
Amino end
Amino acid
subunits
Carboxyl end
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
LE 5-20b
2o structure
 pleated sheet
Amino acid
subunits
 helix
Four Levels of Protein Structure
•
Primary structure (1o)
–
•
Secondary structure (2o)

–
•
unique sequence of amino acids, like letters in a word
-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
LE 5-20d
Hydrophobic
interactions and
van der Waals
interactions
Polypeptide
backbone
Hydrogen
bond
Disulfide bridge
Ionic bond
Four Levels of Protein Structure
•
Primary structure (1o)
–
•
Secondary structure (2o)

–
•
unique sequence of amino acids, like letters in a word
-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
LE 5-20e
Polypeptide
chain
 Chains
Iron
Heme
Polypeptide chain
Collagen
 Chains
Hemoglobin
LE 5-20
 pleated sheet
+H
3N
Amino end
Amino acid
subunits
 helix
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
LE 5-21a
Normal RBC
Sickled RBC
10 µm
Normal cells are
full of individual
hemoglobin
molecules, each
carrying oxygen.
10 µm
Fibers of abnormal
hemoglobin deform
cell into sickle
shape.
LE 5-21b
One Amino Acid Substitution: Huge Effect!
Sickle-cell hemoglobin
Normal hemoglobin
Primary
structure
Val
His
1
2
Leu
Thr
3
4
Pro
Glu
5
6
Secondary
and tertiary
structures
7
 subunit
Quaternary Normal
hemoglobin
structure
(top view)
Primary
structure
Secondary
and tertiary
structures
Molecules do
not associate
with one
another; each
carries oxygen.
His
Leu
Thr
Pro
Val
Glu
1
2
3
4
5
6
7
Exposed
hydrophobic
region
 subunit

Quaternary
structure

Val


Function
Glu
Sickle-cell
hemoglobin


Function
Molecules
interact with
one another to
crystallize into
a fiber; capacity
to carry oxygen
is greatly reduced.


Environment Affects Protein Structure & Function
?
pH
salt concentration
temperature
other environmental factors
Extreme conditions cause
unraveling of protein structure:denaturation
LE 5-22
Caused by, for example, high temperature (100oC)
Denaturation
Normal protein
Denatured protein
Renaturation
Lowered Temp (37oC)
Proper Protein-Folding
• Chaperonins
– protein complexes that assist in the proper folding
of other proteins
LE 5-23a
Cap
Hollow
cylinder
Chaperonin
(fully assembled)
LE 5-23b
Model
Polypeptide
Steps of Chaperonin
Action:
An unfolded polypeptide enters the
cylinder from one
end.
Correctly
folded
protein
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.
Techniques to Determine Protein Structure
• X-ray crystallography (need to make
protein crystals)
• Nuclear magnetic resonance (NMR)
spectroscopy (not dependent on making
protein crystals)
How is the sequence of proteins determined?
-encoded in DNA
- two step process to decode
1. DNA is transcribed into mRNA
2. mRNA is translated into polypetide
More later