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Proteins
Chapter 22
Proteins
(Greek = “of first importance”)
Functions:
– Structure - skin, bones, hair, fingernails
– Catalysis - biological catalysts are enzymes
– Movement - muscle: actin and myosin
– Transport - hemoglobin, transport thru
membranes
Proteins
Functions:
– Hormones - insulin, oxytocin, HGH, etc.
– Protection - antigen-antibody reactions,
fibrinogen in clotting
– Storage - casein in milk, ovalbumin in eggs,
ferritin in liver-stores iron
– Regulation - control in expression of genes
Proteins
• Protein types:
– 9000 different proteins in a cell
– Individual human being >100,000 different
– Fibrous Protein
• Insoluble in H2O
• Used mainly for structural purposes
– Globular Protein
• Partly soluble in H2O
• Usually not used for structural purposes
Proteins are Natural Polymers
• Proteins are constructed in the body from
many repeating units call amino acids
• Just like other polymers the amino acids
(monomers) are joined together to make long
chains (polymers) – but we call them
proteins instead
• All of the polymer information applies to
proteins – cross linking, rings, polarity etc.
Amino Acids
• The Building Blocks of proteins
– Contains an amino group and an acid group
– Nature synthesizes about 20 common AA
– All but one (proline) fit this formula:
– AA Proline:
H
R
C
COOH
COOH
N
proline
NH 2
H
Amino Acids
• Amino Acids (AA)
– The twenty common are Called alpha amino
acids
– One and three letter codes given to 20
common AA
– All but glycine (where R=H)
exist as a pair of enantiomers
• nature usually produces the
L amino acid
LOOK IN THE BOOK
H
R
C
COOH
NH 2
Amino Acids
• Amino Acids (AA)
– Sometimes classified
as AA with:
•
•
•
•
nonpolar R groups
polar but neutral R groups
acidic R groups
basic R groups
Zwitterions
• An acid -COOH and
an amine -NH2 group
cannot coexist
• The H+ migrates to the
-NH2 group
• COO- and NH3+ are
actually present, called
a “Zwitterion”
Zwitterions
• Zwitterion = compound where both a
positive charge and a negative charge
exist on the same molecule
• AA are ionic compounds
• They are internal salts
• In solution their form changes
depending on the pH
AA’s
Zwitterions
pH = 1-5
pH = 10-14
more basic
more acidic
excess H+
excess OH-
H
R
C
H
H
COOH
NH 3
+
R
C
COO-
NH 3+
R
C
COO-
NH 2
AA’s
Zwitterions
pH = 1-5
pH = 10-14
more basic
more acidic
excess H+
H
R
C
COOH
NH 3 +
at pI
(isoelectric
point)
charge = 0
H
R
C
COO-
NH 3+
excess OHH
R
C
COO-
NH 2
AA’s
pI
• The pI is the “isoelectric point”
• The pI is the pH where
NO charge is on the AA:
at pI
charge = 0
(Not necessarily
at a neutral pH)
H
R
C
COO-
NH 3+
Cysteine
• The AA Cysteine exists as a dimer:
H
2
HS
CH 2 C
COOH
NH 2
cysteine
[O]
[H]
H
HCOO
H
C CH 2 S S CH 2 C
NH 2
cystine
COOH
NH 2
a disulfide linkage
AA’s
Peptides
• AA are also called peptides
• They can be combined to form...
H
H2 N
O
CH3 O
CH C OH + H2N CH C OH
glycine
alanine
-H2O
AA’s
Peptides
• AA are also called peptides
• They can be combined to form a dipeptide.
H
H2 N
O
CH3 O
CH C OH + H2N CH C OH
glycine
alanine
H
H2 N
O
CH C
-H2O
CH3 O
NH CH C OH
a peptide bond
Peptides
• Known as a “dipeptide”
H
H2 N
amine
end
O
CH C
CH3 O
NH CH C OH
a peptide bond
glycylalanine (Gly-Ala), a dipeptide
acid
end
Peptides
• Glycylalanine is not the same as Alanylglycine
H
H2 N
O
CH3 O
CH C
NH CH C OH
glycylalanine
CH3 O
H2 N
CH C
H
O
NH CH C OH
alanylglycine
Peptides
• Synthesis of Alanylglycine
CH3 O
H2N
CH C OH
alanine
H
+ H2N
O
CH C OH
-H2 O
glycine
CH3 O
H2 N
CH C
H
O
NH CH C OH
alanylglycine
Peptides
• Addition of peptides (head to tail)
– Formation of:
• dipeptides
• tripeptides
• tetrapeptides
• pentapeptides
• polypeptides
• PROTEINS
AA’s
Student Practice
• Show the product for the following
combination of amino acids
Glu – Pro – His
Pro – Asn – Leu
Val – Ala – Trp
http://www.youtube.com/watch?v=va0DNJId
_CM
Proteins
• Proteins usually contain about 30+ AA
• AA known as residues
– One letter abbreviations
• G, A, V, L
– Three letter abbreviations
• Gly, Ala, Val, Leu
• N terminal AA (amine end) on LEFT
• C terminal AA (carboxyl end) on RIGHT
glycylalanine
Gly-Ala G-A
AA’s
Polypeptides
side chains
• Polypeptides
R
R
R
R
R
R
N
CH C
N
CH C
N
CH C
N
CH C
N
CH C
N
CH C
H
O
H
O
H
O
H
O
H
O
H
O
amino acid
residues
peptide bonds
peptide bonds
AA’s
Solubility
• Polypeptides or Proteins
– If there is a charge on a polypeptide, it is
more soluble in aqueous solution
– If there is NO CHARGE (neutral at pI), it is
LEAST SOLUBLE in solution
H
R
C
H
COOH
R
C
COO-
NH 3 +
NH 2
charged
charged
Protein Structure
• Primary Structure
1o
– Linear sequence of AA
• Secondary Structure
2o
– Repeating patterns ( helix,  pleated sheet)
• Tertiary Structure
3o
– Overall conformation of protein
• Quaternary Structure
4o
– Multichained protein structure
Protein Structure
• Primary Structure
1o
– Linear sequence of AA
R
R
R
R
R
R
N
CH C
N
CH C
N
CH C
N
CH C
N
CH C
N
CH C
H
O
H
O
H
O
H
O
H
O
H
O
AA 1
AA 2
AA 3
AA 4
AA 5
AA 6
With any 6 AA residues,
the number of possible combinations is
6 x 6 x 6 x 6 x 6 x 6 = 46656
AA’s
Protein Structure
• Primary Structure
R
R
R
R
R
R
N
CH C
N
CH C
N
CH C
N
CH C
N
CH C
N
CH C
H
O
H
O
H
O
H
O
H
O
H
O
AA 1
AA 2
AA 3
AA 4
AA 5
AA 6
With any 6 of the 20 common AA residues,
the number of possible combinations is
20 x 20 x 20 x 20 x 20 x 20 = 64,000,000
(and this is not nearly large enough to be a protein!)
AA’s
Protein Structure
• Primary Structure
– A typical protein could have 60 AA residues.
This would have 2060 possible primary
sequences.
2060 = 1078
This results in more possibilities for this
small protein than there are atoms in the
universe!
Protein Structure
• Primary Structure
– Sometimes small changes in the
1o structure do not alter the
biological function, sometimes
they do.
AA’s
Changes and Effect of AA change
• Cattle and hog insulin is used for humans
but is different
• Sickle cell anemia – only one change in an
amino acid – changes the hemoglobin
From yahoo images
youtube
• http://www.youtube.com/watch?v=bCOJkp
L7MVw
Protein Structure
• Secondary Structure
– Repeating patterns
within a region
– Common patterns
 helix
 pleated sheet
– Originally proposed by
• Linus Pauling
• Robert Corey
AA’s
Protein Structure
• Secondary Structure
 helix
– Single protein chain
– Shape maintained by
intramolecular H bonding
between -C=O and H-N– Helical shape
•  helix is clockwise
AA’s
YOUTUBE
http://www.youtube.com/watch?v=yh9Cr5n2
1EE
http://www.youtube.com/watch?v=XKI0le9e2
D8
Protein Structure
• Secondary Structure
 pleated sheet
– Several protein chains
– Shape maintained by
intramolecular H bonding
and other attractive forces
between chains
– Chains run anti-parallel
and make U turns at ends
AA’s
Protein Structure
• Secondary Structure
• Random Coils
– Few proteins have
exclusively  helix or
 pleated sheet
– Many have non-repeating
sections called:
Random Coils
AA’s
Collagen Protein Structure
• Secondary Structure
• Triple Helix of Collagen
– Structural protein of
connective tissues
• bone, cartilage, tendon
• aorta, skin
– About 30% of human
body’s protein
– Triple helix units = tropocollagen
AA’s
Youtube
http://www.youtube.com/watch?v=YmuFI1jtc
8M&feature=PlayList&p=C8887E4E7D367
515&index=0&playnext=1
http://www.youtube.com/watch?v=gXeYf9dL
T3s
Tertiary Structure
– The Three dimensional arrangement of every
atom in the molecule
– Includes not just the peptide backbone but the
side chains as well
– These interactions are responsible for the
overall folding of the protein
– This folding defies its function
and it’s reactivity
AA’s
Tertiary Structure
The Tertiary structure is formed by the following
interactions:
Covalent Bonds
Hydrogen Bonding
Salt Bridges
Hydrophobic Interactions
Metal Ion Coordination
AA’s
Tertiary Structure –Covalent Bonding
• The most common covalent bond in
forming the tertiary structure is the
disufide bond
• It is formed from the disulfide
Interaction of cysteine
H
2
HS
CH2 C
COOH
NH 2
cysteine
[O]
[H]
H
HCOO
H
C CH2 S S CH2 C
NH 2
cystine
COOH
NH 2
Tertiary Structure –Hydrogen Bonding
• Anytime you have a hydrogen connected
to a F O of N – you can get hydrogen
bonding
• These interactions can occure
on the side chain, backbone
or both
Tertiary Structure –Salt Bridge
• Salt bridges are due to charged portions
of the protein.
• Opposite charges will attract and
Form ionic bonds
• Some examples are the
NH3+ and COO- areas of the
protein
Tertiary Structure –hydrophobic interactions
• Because the nonopolar groups will turn
away from the water and the polar
groups toward it, hydrophobic
interactions take place.
• These interactions are strong
enough to help define the
overall structure of a protein
Tertiary Structure –Metal Ion Coordination
• Two side chains with the same charge
would normally repel each other
• However, if a metal is placed between
them, they will coordinate to the meal
and be connected together.
• These metal coordinations are
Important in tertiary structure
formation
Tertiary Structure
Quaternary Structure
– Highest level of organization
– Determines how
subunit fit together
– Example Hemoglobin
(4 sub chains)
• 2 chains 141 AA
• 2 chains 146 AA
- Example - Collagen
Denaturation
• Denaturation
– Any physical or chemical agent that destroys
the conformation of a protein is said to
“denature” it
– Examples:
•
•
•
•
Heat (boil an egg) to gelatin
Addition of 6M Urea (breaks H bonds)
Detergents (surface-active agents)
Reducing agents (break -S-S- bonds)
Denaturation
• Denaturation
– Examples:
• Acids/Bases/Salts (affect salt bridges)
• Heavy metal ions (Hg2+, Pb2+)
– Some denaturation is reversible
• Urea (6M) then add to H2O
– Some is irreversible
• Hard boiling an egg
Denaturation
• Denaturation