Structure

of proteins

AP Biology

Proteins
Most structurally & functionally diverse

group of biomolecules
Function:

involved in almost everything

AP Biology

enzymes
structure (keratin, collagen)
carriers & transport (membrane channels)
receptors & binding (defense)
contraction (actin & myosin)
signaling (hormones)
storage (bean seed proteins)

Proteins
Structure:

monomer = amino acids

20 different amino acids

polymer = polypeptide
protein can be 1 or more polypeptide chains

folded & bonded together

large & complex molecules
complex 3-D shape

AP Biology

Amino acids
Structure:
central carbon
amino group
carboxyl group (acid)
R group (side chain)

variable group
confers unique

chemical properties
of the amino acid

AP Biology

H O
H
| ||
N
C COH
|
H
R

Types of Amino Acids based on

side-chain chemical character :
Non-Polar (8 AAs) :
- hydrocarbon (5 AAs) : Ala, Val,
Leu, Ile, Pro
- aromatic (2 AAs) : Phe, Trp
- thiol ether (1 AA) : Met
Flexible (1 AA) :
- gly flexible because it has no
side chain
Polar (11 AAs) :
- alcohols (3 AAs) :Ser, Thr, Tyr
- thiol (1 AA) : Cys
- amides (2 AAs) : Asn, Gln
- acids (2 AAs) : Asp. Glu
- bases (3 AAs) : Lys, Arg, His
AP Biology

Nonpolar amino acids

nonpolar & hydrophobic

Why are these nonpolar & hydrophobic?

AP Biology

Polar amino acids

polar or charged & hydrophilic

AP Biology

Why are these polar & hydrophillic?

Sulfur containing amino acids

Disulfide bridges

AP Biology

cysteines form cross links

Building proteins
Peptide bonds: dehydration synthesis
linking NH2 of 1 amino acid to
COOH of another
CN bond

AP Biology

peptide
bond

Building proteins
Polypeptide chains
N-terminal = NH2 end
C-terminal = COOH end
repeated sequence (N-C-C) is the
polypeptide backbone

grow in one direction

AP Biology

Protein structure & function

function depends on structure

all starts with the

order of amino acids
what determines that order of

amino acids?

lysozyme: enzyme in tears & mucus that kills bacteria

AP Biology

the 10 glycolytic enzymes

used to breakdown glucose
to make ATP

Protein structure
Protein structure is broken down into four
levels:
primary structure
secondary structure

tertiary structure
quaternary structure

AP Biology

Primary (1) structure

Order of amino acids in chain
amino acid sequence
determined by DNA
slight change in amino acid
sequence can affect proteins
structure & its function

even just one amino acid change

can make all the difference!

AP Biology

Primary (1) structure

Peptides = Mini-Proteins
AP Biology

Sickle cell anemia

Glu= GAA or GAG

AP Biology

Val = GUU, GUC, GUA or GUG

Secondary (2) structure

Local folding

Folding along
short sections of
polypeptide
interaction between

adjacent amino
acids
H bonds between
R groups

AP Biology

Tertiary (3) structure

Whole molecule folding

AP Biology

determined by interactions
between R groups
hydrophobic
interactions
effect of water
in cell
anchored by
disulfide bridges
(H & ionic bonds)

Tertiary (3) structure

AP Biology

Quaternary (4) structure

Joins together more than 1 polypeptide chain

only then is it a functional protein

collagen =
skin & tendons

hemoglobin
AP Biology

Quaternary (4) structure

Quaternary (4) structure is the arrangement of

separate polypeptide chains (subunits) relative to

each other joins together more than 1
polypeptide chain. These chains may be identical
to each other, or different from each other. Only
then is it a functional protein
We classify proteins into 2 major groups
according to tertiary (3) and quarternary (4)
structure:
- fibrous
- globular.

AP Biology

Fibrous proteins

In general, fibrous proteins are :

- built up from a single element of secondary structure
- insoluble in water (lots of hydrophobic residues)
- involved in structural roles within the cell
AP Biology

a-keratin - the protein of hair

Right-hand
Left-hand

AP Biology

a-keratin

Hair
Wool
Nails
Claws
Quills
Horn
Hooves
Outer layer of skin

AP Biology

Disulfide bonds

stabilize.
Toughness depends
on amount of
disulfides
Rhinoceros horn,
18% of residues are
Cys in disulfides.

Silk Fibroin
Produced by insects and

spiders.
High tensile strength, but
flexible
Mostly close-packed bsheets
Rich in Ala and Gly
(alternating why?)
No covalent bonds
between strands or
sheets.
Extensive H-bonding and
van der Waals
interactions for strength.

AP Biology

Collagen

Left-hand single helix, 3

residues/turn
1/3 Gly, 1/5 Pro or Hyp
Triplet Gly-X-Pro (or
Gly-X-Hyp) repeats
Supertwisted coiled coil
is right-handed, made
of 3 left-handed achains
Non-standard covalent
x-links.

LH
AP Biology

RH

Collagen

Tendons
Cartilage
Bone matrix
Cornea of the eye
Lungs

> 30 structural variants

of collagen in a mammal
Different tissues have
different collagens.
Diseases of collagen
abnormalities

Ehler-Danlos
syndrome
Osteogenesis
imperfecta.

AP Biology

Globular proteins

Compact
Made up of regions of

a-helix, b-sheets, bturns, and others as

well
Stability primarily
results from
hydrophobic core; also
H-bonding.

Carbonic anhydrase
AP Biology

9/16/05

Myoglobin, a globular protein

A small protein (153 aas, 16.7 kD)

Contains a heme prosthetic group
Stores oxygen in muscle cells
It is mostly a-helix (78% of its aas are in
the 8 segments, from 7 to 23 aas long),
linked by turns (some of them b)
Much of its stability comes from hydrophobic
interactions

AP Biology

9/16/05

Myoglobin structure
Ball-and-stick:

AP Biology

Ribbon:

Ribbon diagram shows backbone conformation.

.

Domains

Troponin C.
Note : 1 polypeptide chain!
AP Biology

Domains
Domains

are usually > 100 aas

Domains are often functional and comprise a
contiguous segment of the full protein
Domain structure is thought to reflect the
evolutionary fusion of functional elements to
create novel new proteins
Domains are stable, self-folding
substructures

Fig. 4-19

AP Biology

9/16/05

Multimers

Multimers are assembled from multiple

polypeptide chains.
Have we learned about any multimers yet?
One of them: hemoglobin.

AP Biology

9/16/05

Protein structure (review)

R groups
hydrophobic interactions,
disulfide bridges

multiple
polypeptides
hydrophobic
interactions

1
aa sequence
peptide bonds
determined
by DNA
AP Biology

2
R groups
H bonds

Protein Folding
Tujuan folding :
Untuk menghasilkan suatu bentuk unik yang
compatibel dengan fungsi biologis spesifik

Untuk memperoleh bentuk yang stabil secara

kimia
The driving force for protein folding is
provided by water
Protein folding is a bit like a drop of oil in
water

AP Biology

Chaperonin proteins
Guide protein folding

AP Biology

provide shelter for folding polypeptides

keep the new protein segregated from
cytoplasmic influences

Protein models
Protein structure visualized by
X-ray crystallography
extrapolating from amino acid sequence
computer modelling

lysozyme
AP Biology

Denature a protein
Disrupt 3 structure
pH

salt

temperature

unravel or denature protein

disrupts H bonds, ionic bonds &

disulfide bridges

Some proteins can

return to their
functional shape
after denaturation,
many cannot
AP Biology

Homologous Proteins
have similar function and similar AA sequence as
well as 3D shape
Invariant AAs are involved in function or bonding
critical to the protein's shape
Variable AAs are only parts of the protein's
framework
analyze the AA sequences of the same protein from
different organisms
example is the electron carrying protein of
mitochondria called Cytochrome c which has a
bound heme-Fe so it has a red-orange color like
hemoglobin
AP Biology

Cytochrome C
Since Cytochrome c
appears to be required
for survival of
eukaryotic organisms,
change in its amino
acid sequence, which
reflects change in its
gene, can be used to
measure change in
species during
evolution.

Structural model of Cytochrome C showing

a few of its invariant amino acids
AP Biology

AMINO ACID SEQUENCE OF CYTOCHROME C

These invariant AA are absolutely required for

functionality of cytochrome c
AP Biology

PHYLOGENETIC TREE OF SPECIES BASED ON THE

AMINO ACID SEQUENCE OF CYTOCHROME C

AP Biology

SIMILAR FUNCTION - DIFFERENT SEQUENCE

Cth: Dehydrogenases are enzymes transferring electrons from a
reduced substrate to NAD+ -- a cellular electron carrier.

3 different dehydrogenases (alcohol dehydrogenase, lactate

dehydrogenase, and glyceraldehyde-phosphate dehydrogenase)
which all use NAD+ as an electron acceptor, but use different
metabolites as the reduced substrate which donates the electrons
to NAD+ making it into NADH:

AP Biology

ENZYMES WITH THE SAME 3-D

SHAPE BUT DIFFERENT FUNCTIONS

These enzymes have no similarity in AA sequence

AP Biology

Lets build some

Proteins!

AP Biology

Structure
of proteins

Proteins
Most structurally & functionally diverse
group of biomolecules
Function:
involved in almost everything

enzymes
structure (keratin, collagen)
carriers & transport (membrane channels)
receptors & binding (defense)
contraction (actin & myosin)
signaling (hormones)
storage (bean seed proteins)

Proteins
Structure:
monomer = amino acids
20 different amino acids

polymer = polypeptide
protein can be 1 or more polypeptide chains folded
& bonded together
large & complex molecules
complex 3-D shape

 Structure:

Amino acids

central carbon
amino group
carboxyl group (acid)
R group (side chain)

variable group
confers unique

chemical properties
of the amino acid

H
O
H
|
||
N
CCOH
|
H
R

Types of Amino Acids based on side-chain chemical

character :

Non-Polar (8 AAs) :
- hydrocarbon (5 AAs) : Ala, Val,
Leu, Ile, Pro
- aromatic (2 AAs) : Phe, Trp
- thiol ether (1 AA) : Met
Flexible (1 AA) :
- gly flexible because it has no
side chain
Polar (11 AAs) :
- alcohols (3 AAs) :Ser, Thr, Tyr
- thiol (1 AA) : Cys
- amides (2 AAs) : Asn, Gln
- acids (2 AAs) : Asp. Glu
- bases (3 AAs) : Lys, Arg, His

Nonpolar amino acids

nonpolar & hydrophobic

Why are these nonpolar & hydrophobic?

Polar amino acids

polar or charged & hydrophilic

Why are these polar & hydrophillic?

Sulfur containing amino acids

Disulfide bridges
cysteines form cross links

Building proteins
Peptide bonds: dehydration synthesis
linking NH2 of 1 amino acid to
COOH of another
CN bond

peptide
bond

Building proteins
Polypeptide chains
N-terminal = NH2 end
C-terminal = COOH end
repeated sequence (N-C-C) is the
polypeptide backbone
grow in one direction

Protein structure & function

function depends on structure
all starts with the
order of amino acids
what determines that order of
amino acids?

lysozyme: enzyme in tears & mucus that kills bacteria

the 10 glycolytic enzymes
used to breakdown glucose
to make ATP

Protein structure
Protein structure is broken down into four
levels:
primary structure
secondary structure

tertiary structure
quaternary structure

Primary (1) structure

Order of amino acids in chain
amino acid sequence determined
by DNA
slight change in amino acid
sequence can affect proteins
structure & its function
even just one amino acid change can
make all the difference!

Primary (1)
structure

Peptides = Mini-Proteins

Sickle cell anemia

Glu= GAA or GAG

Val = GUU, GUC, GUA or GUG

Secondary (2) structure

Local folding
Folding along short
sections of
polypeptide
interaction between
adjacent amino acids
H bonds between
R groups

Tertiary (3) structure

Whole molecule folding
determined by interactions
between R groups
hydrophobic
interactions
effect of water
in cell
anchored by
disulfide bridges
(H & ionic bonds)

Tertiary (3) structure

Quaternary (4) structure

Joins together more than 1 polypeptide chain
only then is it a functional protein

collagen =
skin & tendons

hemoglobin

Quaternary (4) structure

Quaternary (4) structure is the arrangement of separate
polypeptide chains (subunits) relative to each other
joins together more than 1 polypeptide chain. These
chains may be identical to each other, or different from
each other. Only then is it a functional protein
We classify proteins into 2 major groups according to
tertiary (3) and quarternary (4) structure:
- fibrous
- globular.

Fibrous proteins

In general, fibrous proteins are :

- built up from a single element of secondary structure
- insoluble in water (lots of hydrophobic residues)
- involved in structural roles within the cell

a-keratin - the protein of hair

Right-hand
Left-hand

a-keratin

Hair
Wool
Nails
Claws
Quills
Horn
Hooves
Outer layer of skin

Disulfide bonds

stabilize.
Toughness depends
on amount of
disulfides
Rhinoceros horn,
18% of residues are
Cys in disulfides.

Silk Fibroin
Produced by insects and
spiders.
High tensile strength, but
flexible
Mostly close-packed bsheets
Rich in Ala and Gly
(alternating why?)
No covalent bonds between
strands or sheets.
Extensive H-bonding and
van der Waals interactions
for strength.

Collagen
Left-hand single helix, 3
residues/turn
1/3 Gly, 1/5 Pro or Hyp
Triplet Gly-X-Pro (or GlyX-Hyp) repeats
Supertwisted coiled coil
is right-handed, made of
3 left-handed a-chains
Non-standard covalent xlinks.
LH

RH

Collagen

Tendons
Cartilage
Bone matrix
Cornea of the eye
Lungs

> 30 structural variants

of collagen in a mammal
Different tissues have
different collagens.
Diseases of collagen
abnormalities

Ehler-Danlos
syndrome
Osteogenesis
imperfecta.

Globular proteins
Compact
Made up of regions of ahelix, b-sheets, b-turns,
and others as well
Stability primarily
results from
hydrophobic core; also
H-bonding.

Carbonic anhydrase
9/16/05

Myoglobin, a globular protein

A small protein (153 aas, 16.7 kD)

Contains a heme prosthetic group
Stores oxygen in muscle cells
It is mostly a-helix (78% of its aas are in the 8
segments, from 7 to 23 aas long), linked by turns
(some of them b)
Much of its stability comes from hydrophobic
interactions

9/16/05

Myoglobin structure

Ball-and-stick

Ribbon:

Ribbon diagram shows backbone conformation.

.

Domains

Troponin C.
Note : 1 polypeptide chain!

Domains
Domains

are usually > 100 aas

Domains are often functional and comprise a
contiguous segment of the full protein
Domain structure is thought to reflect the
evolutionary fusion of functional elements to
create novel new proteins
Domains are stable, self-folding
substructures

Fig. 4-19

9/16/05

Multimers
Multimers are assembled from multiple polypeptide
chains.
Have we learned about any multimers yet?
One of them: hemoglobin.

9/16/05

Protein structure (review)

R groups
hydrophobic interactions,
disulfide bridges
3

multiple
polypeptides
hydrophobic
interactions

1
aa sequence
peptide bonds
determined
by DNA

R groups
H bonds

Protein Folding
Tujuan folding :
Untuk menghasilkan suatu bentuk unik yang
compatibel dengan fungsi biologis spesifik

Untuk memperoleh bentuk yang stabil secara

kimia
The driving force for protein folding is
provided by water
Protein folding is a bit like a drop of oil in
water

Chaperonin proteins
Guide protein folding
provide shelter for folding polypeptides
keep the new protein segregated from cytoplasmic
influences

Protein models
Protein structure visualized by
X-ray crystallography
extrapolating from amino acid sequence
computer modelling

lysozyme

Denature a protein
Disrupt 3 structure
pH
temperature

salt

unravel or denature protein

disrupts H bonds, ionic bonds &

disulfide bridges

Some proteins can

return to their
functional shape
after denaturation,
many cannot

Homologous Proteins
have similar function and similar AA sequence as
well as 3D shape
Invariant AAs are involved in function or bonding
critical to the protein's shape
Variable AAs are only parts of the protein's
framework
analyze the AA sequences of the same protein from
different organisms
example is the electron carrying protein of
mitochondria called Cytochrome c which has a
bound heme-Fe so it has a red-orange color like
hemoglobin

Cytochrome C
Since Cytochrome c
appears to be required
for survival of
eukaryotic organisms,
change in its amino
acid sequence, which
reflects change in its
gene, can be used to
measure change in
species during
evolution.
Structural model of Cytochrome C showing a few
of its invariant amino acids

AMINO ACID SEQUENCE OF CYTOCHROME C

These invariant AA are absolutely required for

functionality of cytochrome c

PHYLOGENETIC TREE OF SPECIES BASED ON THE

AMINO ACID SEQUENCE OF CYTOCHROME C

SIMILAR FUNCTION - DIFFERENT SEQUENCE

Cth: Dehydrogenases are enzymes transferring electrons from a
reduced substrate to NAD+ -- a cellular electron carrier.

3 different dehydrogenases (alcohol dehydrogenase, lactate

dehydrogenase, and glyceraldehyde-phosphate dehydrogenase)
which all use NAD+ as an electron acceptor, but use different
metabolites as the reduced substrate which donates the electrons
to NAD+ making it into NADH:

ENZYMES WITH THE SAME 3-D SHAPE BUT

DIFFERENT FUNCTIONS

These enzymes have no similarity in AA sequence

Lets build some

Proteins!