Transcript Protein Structure - HCC Learning Web

Chapter 3
The Structure and Function of
Large Biological Molecules
Protein
The Molecules of Life
• All living things are made up of four classes
of large biological molecules: carbohydrates,
lipids, proteins, and nucleic acids
• Macromolecules are large molecules
composed of thousands of covalently
connected atoms
• Molecular structure and function are
inseparable
Macromolecules are polymers, built from
monomers
• A polymer is a long molecule consisting of
many similar building blocks
• These small building-block molecules are
called monomers
• Three of the four classes of life’s organic
molecules are polymers
– Carbohydrates
– Proteins
– Nucleic acids
Which group of large biological
molecules is not synthesized via
dehydration reactions?
a)
b)
c)
d)
polysaccharides
lipids
proteins
nucleic acids
Which group of large biological
molecules is not synthesized via
dehydration reactions?
a)
b)
c)
d)
polysaccharides
lipids
proteins
nucleic acids
The Synthesis and Breakdown of Polymers
• A dehydration reaction occurs when two
monomers bond together through the loss of a
water molecule
(a) Dehydration reaction: synthesizing a polymer
1
2
3
Unlinked monomer
Short polymer
Dehydration removes
a water molecule,
forming a new bond.
1
2
3
Longer polymer
4
The Synthesis and Breakdown of Polymers
• Polymers are disassembled to monomers by
hydrolysis, a reaction that is essentially the
reverse of the dehydration reaction
(b) Hydrolysis: breaking down a polymer
1
2
3
Hydrolysis adds
a water molecule,
breaking a bond.
1
2
3
4
The Diversity of Polymers
• Each cell has thousands of different
macromolecules
• Macromolecules vary among cells of an
organism, vary more within a species, and
vary even more between species
• An immense variety of polymers can be built
from a small set of monomers
HO
Protein
Proteins include a diversity of structures,
resulting in a wide range of functions
• Proteins account for more than 50% of the dry
mass of most cells
• Protein functions include structural support,
storage, transport, cellular communications,
movement, and defense against foreign
substances
Amino acid (aa)
aa
aa
aa
aa
aa
Protein
aa
aa
aa
Amino Acid Monomers
• Amino acids are organic molecules with
carboxyl and amino groups
• Amino acids differ in their properties due to
differing side chains, called R groups
Side chain (R group)
 carbon
Amino
group
Carboxyl
group
Functional Groups Affect Reactivity
• R-groups differ in their size, shape, reactivity, and
interactions with water.
1. Nonpolar R-groups: hydrophobic; do not form
hydrogen bonds; insoluble in water
2. Polar R-groups: hydrophilic; form hydrogen bonds;
readily dissolve in water
• Amino acids with hydroxyl, amino, carboxyl, or sulfhydryl
functional groups in their side chains are more chemically
reactive than those with side chains composed of only
carbon and hydrogen atoms.
The Structure of Amino Acids
• In water (pH 7), the amino and carboxyl groups
ionize to NH3+ and COO–, respectively—this helps
amino acids stay in solution and makes them
more reactive.
Nonpolar side chains; hydrophobic
Side chain
(R group)
Glycine
(Gly or G)
Alanine
(Ala or A)
Methionine
(Met or M)
Isoleucine
(Ile or I)
Leucine
(Leu or L)
Valine
(Val or V)
Phenylalanine
(Phe or F)
Tryptophan
(Trp or W)
Proline
(Pro or P)
Polar side chains; hydrophilic
Serine
(Ser or S)
Threonine
(Thr or T)
Cysteine
(Cys or C)
Electrically charged side chains; hydrophilic
Tyrosine
(Tyr or Y)
Asparagine
(Asn or N)
Glutamine
(Gln or Q)
Basic (positively charged)
Acidic (negatively charged)
Aspartic acid
(Asp or D)
Glutamic acid
(Glu or E)
Lysine
(Lys or K)
Arginine
(Arg or R)
Histidine
(His or H)
Amino Acid Polymers
• Amino acids are linked by peptide bonds
• A polypeptide is a polymer of amino acids
• Polypeptides range in length from a few to
more than a thousand monomers
• Each polypeptide has a unique linear
sequence of amino acids, with a carboxyl end
(C-terminus) and an amino end (N-terminus)
Polypeptides
• Polypeptides are unbranched polymers built
from the same set of 20 amino acids
• A protein is a biologically functional molecule
that consists of one or more polypeptides
Amino acid (aa)
aa
aa
aa
aa
aa
aa
aa
aa
Polypeptide (Protein)- Oligonuclotide versus protein
• Polymerization requires energy and is nonspontaneous.
• Monomers polymerize through condensation (dehydration)
reactions, which release a water molecule.
• Hydrolysis is the reverse reaction, which breaks polymers apart
by adding a water molecule.
Condensation reactions
bond the carboxyl group
of one amino acid to the
amino group of another
to form a peptide bond
Peptide bond
New peptide
bond forming
Side
chains
Backbone
Amino end
(N-terminus)
Peptide
bond
Carboxyl end
(C-terminus)
• Within the polypeptide, the peptide bonds form a
“backbone” with three key characteristics:
1. R-group orientation
•
Side chains can interact with each other or water.
2. Directionality
•
•
Free amino group, on the left, is called the N-terminus.
Free carboxyl group, on the right, is called the Cterminus.
3. Flexibility
•
Single bonds on either side of the peptide bond can
rotate, making the entire structure flexible.
What do proteins do?
– Catalysis – enzymes speed up chemical reactions.
– Defense – antibodies and complement proteins
attack pathogens.
– Movement – motor and contractile proteins move
the cell or molecules within the cell.
– Signaling – proteins convey signals between cells.
– Structure – structural proteins define cell shape and
comprise body structures.
– Transport – transport proteins carry materials;
membrane proteins control molecular movement into
and out of the cell.
• Enzymes are a type of protein that acts as a
catalyst to speed up chemical reactions
• Enzymes can perform their functions
repeatedly, functioning as workhorses that
carry out the processes of life
How Do Enzymes Work?
• Enzymes bring substrates together in specific positions
that facilitate reactions, and are very specific in which
reactions they catalyze.
• Substrates bind to the enzyme’s active site.
• Many enzymes undergo a conformational change when
the substrates are bound to the active site; this change is
called an induced fit.
• Interactions between the enzyme and the substrate
stabilize the transition state and lower the activation energy
required for the reaction to proceed.
Enzymatic proteins
Defensive proteins
Function: Selective acceleration of chemical reactions
Example: Digestive enzymes catalyze the hydrolysis
of bonds in food molecules.
Function: Protection against disease
Example: Antibodies inactivate and help destroy
viruses and bacteria.
Antibodies
Enzyme
Virus
Bacterium
Storage proteins
Transport proteins
Function: Storage of amino acids
Function: Transport of substances
Examples: Hemoglobin, the iron-containing protein of
vertebrate blood, transports oxygen from the lungs to
other parts of the body. Other proteins transport
molecules across cell membranes.
Examples: Casein, the protein of milk, is the major
source of amino acids for baby mammals. Plants have
storage proteins in their seeds. Ovalbumin is the
protein of egg white, used as an amino acid source
for the developing embryo.
Transport
protein
Ovalbumin
Amino acids
for embryo
Cell membrane
Hormonal proteins
Receptor proteins
Function: Coordination of an organism’s activities
Example: Insulin, a hormone secreted by the
pancreas, causes other tissues to take up glucose,
thus regulating blood sugar concentration
Function: Response of cell to chemical stimuli
Example: Receptors built into the membrane of a
nerve cell detect signaling molecules released by
other nerve cells.
High
blood sugar
Insulin
secreted
Normal
blood sugar
Receptor
protein
Signaling
molecules
Contractile and motor proteins
Structural proteins
Function: Movement
Examples: Motor proteins are responsible for the
undulations of cilia and flagella. Actin and myosin
proteins are responsible for the contraction of
muscles.
Function: Support
Examples: Keratin is the protein of hair, horns,
feathers, and other skin appendages. Insects and
spiders use silk fibers to make their cocoons and webs,
respectively. Collagen and elastin proteins provide a
fibrous framework in animal connective tissues.
Actin
Myosin
Collagen
Muscle tissue
100 m
Connective
tissue
60 m
What do proteins look like?
Protein Structure and Function
• A functional protein consists of one or more
polypeptides precisely twisted, folded, and
coiled into a unique shape
Groove
Groove
(a) A ribbon model
(b) A space-filling model
• The sequence of amino acids determines a
protein’s three-dimensional structure
• A protein’s structure determines its function
Antibody protein
Protein from flu virus
Four Levels of Protein Structure
• The primary structure of a protein is its unique
sequence of amino acids
• Secondary structure, found in most proteins,
consists of coils and folds in the polypeptide
chain (back bone)
• Tertiary structure is determined by interactions
among various side chains (R groups)
• Quaternary structure results when a protein
consists of multiple polypeptide chains
Primary structure
Amino
acids
Amino end
Primary structure of transthyretin
Carboxyl end
• Primary structure, the sequence of amino
acids in a protein (one polypeptide chain), is
like the order of letters in a long word
• Primary structure is determined by inherited
genetic information
Tertiary
structure
Secondary
structure
Quaternary
structure
 helix
Hydrogen bond
 pleated sheet
 strand
Hydrogen
bond
Transthyretin
polypeptide
Transthyretin
protein
• The coils and folds of secondary structure result from
hydrogen bonds between repeating constituents of a
polypeptide chain backbone
• Typical secondary structures are:  helix and 
pleated sheet
• A polypeptide must bend to allow this hydrogen bonds
form.
• Secondary structure depends on the primary structure.
• The large number of hydrogen bonds in a protein’s
secondary structure increases its stability.
Secondary structure
 helix
 pleated sheet
Hydrogen bond
 strand, shown as a flat
arrow pointing toward
the carboxyl end
Hydrogen bond
• Tertiary structure is determined by
interactions between R groups, rather than
interactions between backbone constituents
• These interactions between R groups include
hydrogen bonds, ionic bonds, hydrophobic
interactions, and van der Waals interactions
• Strong covalent bonds called disulfide
bridges may reinforce the protein’s structure
These contacts cause the backbone to bend and fold, and contribute to the
distinctive three-dimensional shape of the polypeptide.
Hydrogen
bond
Hydrophobic
interactions and
van der Waals
interactions
Disulfide
bridge
Ionic bond
Polypeptide
backbone
Quaternary Structure
• Many proteins contain several distinct polypeptide subunits
that interact to form a single structure; the bonding of two
or more subunits produces quaternary structure.
Quaternary structure
Transthyretin
protein
(four identical
polypeptides)
Heme
Iron
 subunit
 subunit
 subunit
 subunit
Hemoglobin
• Quaternary structure results when two or
more polypeptide chains form one
macromolecule
• Collagen is a fibrous protein consisting of three
polypeptides coiled like a rope
• Hemoglobin is a globular protein consisting of
four polypeptides: two alpha and two beta
chains
Collagen
Summary of Protein Structure
• Note that protein structure is hierarchical.
– Quaternary structure is based on tertiary structure, which
is based in part on secondary structure.
– All three of the higher-level structures are based on
primary structure.
• The combined effects of primary, secondary, tertiary, and
sometimes quaternary structure allow for amazing diversity
in protein form and function.
Sickle-Cell Disease: A Change in Primary
Structure
• A slight change in primary structure can affect
a protein’s structure and ability to function
• Sickle-cell disease, an inherited blood
disorder, results from a single amino acid
substitution in the protein hemoglobin
Sickle-cell hemoglobin
Normal hemoglobin
Primary
Structure
1
2
3
4
5
6
7
Secondary
and Tertiary
Structures
Quaternary
Structure
Function
Molecules do not
associate with one
another; each carries
oxygen.
Normal
hemoglobin
 subunit

Red Blood
Cell Shape

10 m


1
2
3
4
5
6
7
Exposed
hydrophobic
region
Sickle-cell
hemoglobin

 subunit

Molecules crystallize
into a fiber; capacity
to carry oxygen is
reduced.


10 m
Protein Structure
The sickle-cell hemoglobin
mutation alters what level(s)
of protein structure?
a)
b)
c)
d)
e)
primary
tertiary
quarternary
all of the above
primary and tertiary
structures only
Protein Structure
The sickle-cell hemoglobin
mutation alters what level(s)
of protein structure?
a)
b)
c)
d)
e)
primary
tertiary
quarternary
all of the above
primary and tertiary
structures only
What Determines Protein Structure?
• In addition to primary structure, physical and
chemical conditions can affect structure
• Alterations in pH, salt concentration,
temperature, or other environmental factors
can cause a protein to unravel
• This loss of a protein’s native structure is
called denaturation
• A denatured protein is biologically inactive
tu
Normal protein
Denatured protein
Protein Folding in the Cell
• It is hard to predict a protein’s structure from
its primary structure
• Most proteins probably go through several
stages on their way to a stable structure
• Chaperonins are protein molecules that
assist the proper folding of other proteins
(Heat Shock protein family-HSP)
• Diseases such as Alzheimer’s, Parkinson’s,
and mad cow disease are associated with
misfolded proteins
Polypeptide
Correctly
folded
protein
Cap
Hollow
cylinder
Chaperonin
(fully assembled)
Steps of Chaperonin
Action:
1 An unfolded polypeptide enters the
cylinder from
one end.
2 The cap attaches, causing 3 The cap comes
the cylinder to change
off, and the
shape in such a way that
properly folded
it creates a hydrophilic
protein is
environment for the
released.
folding of the polypeptide.
• Scientists use X-ray crystallography to
determine a protein’s structure
• Another method is nuclear magnetic
resonance (NMR) spectroscopy, which does
not require protein crystallization
• Bioinformatics uses computer programs to
predict protein structure from amino acid
sequences
EXPERIMENT
Diffracted
X-rays
X-ray
source X-ray
beam
Crystal
Digital detector
X-ray diffraction
pattern
RESULTS
RNA
DNA
RNA
polymerase II
Was the First Living Entity a Protein
(Miller’s Experiment)?
• Several observations argue that the first self-replicating
molecule on Earth was a protein:
1. Amino acids were abundant in the prebiotic soup.
2. Proteins are the most efficient catalysts known.
3. A self-replicating molecule had to act as a
catalyst for the assembly and
polymerization of its copy.
• However, the first self-replicator probably
needed to have a mold or a template (something
not found in proteins).