Download Lecture 4 - Biological Molecules Part II

Class III:
• Store, transmit, and express hereditary
information
• Composed of DNA and RNA
– DNA contains a (deoxyribose) sugar-phosphate
backbone and nucleotides
– RNA contains a (ribose) sugar-phosphate backbone
and nucleotides
• Each nucleotide consists of a nitrogenous base, a pentose
sugar, and one or more phosphate groups
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Structure of DNA
• DNA molecules have two
polynucleotides spiraling
around an imaginary axis,
forming a double helix
• Composed of nitrogenous
base, sugar, and phosphate
group
• One DNA molecule can be
millions of nucleotides long
and contain many genes
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Structure of DNA
Nucleotide = nucleoside + phosphate group
Nucleoside = purine or pyrimidine + sugar
Monomer
Nucleotides are linked together by
phosphodiester bonds
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Structure of Nucleotides
• Two types of nitrogenous
bases
– Pyrimidines (cytosine,
thymine, and uracil) have a
single six-membered ring
– Purines (adenine and
guanine) have a sixmembered ring fused to a
five-membered ring
• In DNA, the sugar is
deoxyribose; in RNA, the
sugar is ribose
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Structure of sugar-phosphate backbone
•
•
The two backbones run in opposite 5→ 3
directions from each other, an
arrangement referred to as antiparallel
The nucleotide monomers are linked by
phosphodiester bonds
This 3’-5’
strand is
absent in
RNA
Phosphodiester bond
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Base-pairing in DNA
• The nitrogenous bases pair with each other through hydrogen
bonding – called complementary base-pairing
– Adenine and thymine base-pair with two hydrogen bonds
– Guanine and cytosine base-pair with three hydrogen bonds
Regions in the
DNA high in G-C
bonds tend to be
more stable
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The 5’-3’ strand of DNA has the nucleic acid
sequence ATGCGTC. What is the sequence of the
complementary 3’-5’strand?
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Structure and function of RNA
• DNA is double-stranded
– Stores genetic information in
the nucleus
• RNA is usually single-stranded
– Transmits genetic information
from inside the nucleus to
outside
• RNA is less stable
– OH groups on the 2’ carbon
make it more vulnerable to
hydrolysis
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RNA can also base-pair with itself
• …Sometimes
• The backbone bends, and the bases on the
single strand will base-pair with themselves
• Only happens in specific circumstances
Base pair joined
by hydrogen
bonding
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 Transfer RNA
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Differences between DNA and RNA
Strand
construction
Nitrogenous
bases
Sugar
Function
Stability
DNA
RNA
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Nucleoside analogs
• Many cancer and antiretroviral drugs are nucleoside
analogs
• They ‘mimic’ the natural nucleoside enough to be
accidentally integrated into DNA by the cell, but are
different enough to cause damage to the DNA
Thymine
5-Fluorouracil, a chemotherapy drug
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Class IV:
• The machinery of the cell
– Protein functions include structural support,
storage, transport, cellular communications,
movement, and defense against foreign
substances
• Most complex biological molecule
• Proteins account for more than 50% of the dry
mass of most cells
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Figure 5.15-a
Examples of Proteins
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
Figure 5.15-b
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
Enzymes: a type of protein
• Enzymes are a type of protein that acts as a
catalyst to speed up chemical reactions
• Enzymes can perform their functions
repeatedly without being used up in a
reaction, functioning as workhorses that carry
out the processes of life
• An enzyme is denoted by the suffix “-ase”
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Amino acids: the monomers of
proteins
• Amino acids are organic molecules with carboxyl and
amino groups
• Amino acids differ in their properties due to differing
side chains, called R groups
• 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
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Structure of amino acids
Side chain (R group)
Amino
group
Carboxyl
group
• Amino acids contain a
carboxyl and amino
groups
• There are 20 amino
acids important to
humans. Each one has
an amino and carboxyl
group, but different R
group
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Amino acid polymers
• Polypeptides are linked by peptide bonds
• 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 (Nterminus)
Peptide bond
N-terminus
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C-terminus
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Figure 5.17
Peptide bond
New peptide
bond forming
Side
chains
Backbone
Amino end
(N-terminus)
Peptide
bond
Carboxyl end
(C-terminus)
How do polypeptides create a 3D shape?
• A protein is made up of one or more polypeptide
chains twisted and folded into a unique 3D shape
• It is the 3D shape that gives the protein its
function
• There are four levels of protein structure:
–
–
–
–
Primary
Secondary
Tertiary
Quaternary
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Primary protein structure
• The sequence of amino acids in a polypeptide chain
• Primary structure is like the order of letters in a long
word
In the structural protein collagen, part of the primary structure is:
gatgapgiag apgfpgarga pgpqgpsgap gp
Glycine – alanine – threonin – glycine – alanine – proline –
glycine – isoleucine – alanine, glycine – alanine – proline –
glycine – phenylalanine – proline – glycine – alanine – etc.
Shorthand version
Written out version
http://www.ncbi.nlm.nih.gov/protein/P0C2W2.2
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Figure 5.20a
Primary structure
Amino
acids
Amino end
Primary structure of transthyretin
Carboxyl end
Secondary protein structure
• Secondary structure is a result of hydrogen
bonding between backbone monomers
warping the polypeptide chain into distinct
patterns
• Typical secondary structures are a coil called
an  helix and a folded structure called a 
pleated sheet
• These ‘typical structures’ are called motifs
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Figure 5.20c
Secondary structure
 helix
 pleated sheet
Hydrogen bond
 strand, shown as a flat
arrow pointing toward
the carboxyl end
Hydrogen bond
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Tertiary protein structure
• 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
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Figure 5.20f
Hydrogen
bond
Hydrophobic
interactions and
van der Waals
interactions
Disulfide
bridge
Ionic bond
Polypeptide
backbone
Figure 5.20e
Tertiary structure
Transthyretin
polypeptide
Quaternary protein structure
• Quaternary structure results when two or
more separate polypeptide chains form one
giant macromolecule
• Composed of repeated ‘chunks’ of tertiary
structure called subunits
• Held together by Van der Waals forces,
hydrogen bonds, and ionic bonds
• Not all proteins have quaternary structure
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Figure 5.20g
Quaternary structure
Transthyretin
protein
(four identical
polypeptides)
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Dimers, trimers, and x-mers, oh my
• A subunit is a repeated tertiary-level structure
• Protein dimers are composed of two subunits
• Trimers are three subunits
Different genes can encode for different subunits of one protein!
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The intermolecular forces in protein
folding
• Primary
– Peptide bonds
• Secondary
– Hydrogen bonding between the backbone atoms
• Tertiary
– Hydrogen bonding, ionic bonding, disulfide bridges,
and Van der Waals forces between the R groups
• Quaternary
– Van der Waals forces, hydrogen bonds, and ionic
bonds between the subunits
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Linking structure back to function
• What is this protein’s function
(enzyme, defense, storage,
transport, etc.)?
• What sort of structure do you
see?
– Secondary
– Tertiary
– Quaternary
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Environmental factors that determine
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
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Denaturation
• When heat, pH, etc. get to be too much, a protein denatures
– Loses its quaternary, tertiary, and sometimes secondary
structure
– Primary structure is only damaged in extreme conditions
– The exact point at which a protein denatures depends on
the protein itself
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Sickle-cell anemia
• A single amino acid change in primary structure can
affect a protein’s structure and ability to function
– HOWEVER if the substitution is similar (a polar a.a. for
another polar a.a. for example) there may be little to no
difference in the final 3D shape
• Sickle-cell disease, an inherited blood disorder,
results from a single amino acid substitution in the
protein hemoglobin
– Hemoglobin very important in oxygen transport by blood
– More common in African Americans, possibly was a
mechanism to prevent malaria infection
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Figure 5.21
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 misfolding
• A special protein class called chaperonins
helps to fold other proteins
• Misfolded proteins are the culprit behind
Alzheimer’s, Parkinson’s, and mad cow disease
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In a protein, a glycine (small, nonpolar amino acid) is
substituted with a tyrosine (very large, polar amino
acid). Describe the changes that might occur to its
primary, secondary, and tertiary structure
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Folding @ Home
• If we can figure out the 3D shape of proteins, we
can manipulate them and more easily find drugs
that target them
• Folding @ Home is a project working towards
elucidating proteins important in Alzheimer’s and
other diseases
• Folding @ Home borrows your computer power
to figure out 3D protein shapes
• There are more possible 3D shapes than there
are atoms in the universe
– LOTS of computing power required!
http://folding.stanford.edu/
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Vocabulary – Part I
• Hydrolysis, dehydration
reaction
• Polymer, monomer
• Monosaccharide,
disaccharide,
polysaccharide
• Glycosidic bond
• Glucose, fructose
• Sucrose, lactose
•  and  glucose
• Amylose, amylopectin,
glycogen
• Fats, glycerol, fatty acids
• Saturated fats,
monounsaturated fats,
polyunsaturated fats
• Cis-trans isomerism
• Hydrogenation
• Cholesterol
• Steroids
• Phospholipid, Phospholipid
bilayer
• Liposome
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Vocabulary – Part II
•
•
•
•
•
•
•
•
•
DNA, RNA
Base pairing
Antiparallel strands
3’ end, 5’ end
Nucleotide, nucleoside
Pyrimidine, purine
Deoxyribose, ribose
A, T, C, G, U
Complementary basepairing
• Phosphodiester bond
• Enzyme
•
•
•
•
•
Protein
Polypeptide
Amino acid
Peptide bond
Primary, secondary, tertiary,
quaternary structure
• Denaturation
• Sickle cell anemia
• Chaperonin
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