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Transcript
Protein Synthesis
James Watson and Francis Crick demonstrating a DNA double helix model.
Importance of Proteins
• Much of the “work” done by the cells and tissues of
the body is actually the result of a protein.
• Examples include:
– Carrier proteins, which facilitate many forms of cell
membrane transport, including endocytosis.
– Recognition proteins, which identify the cell as self to
the immune system.
– Antibodies, which bind to and disable infectious viruses
and bacteria.
– Structural proteins, which make up connective tissues
such as ligaments and tendons.
– Hormones, which deliver messages throughout the body.
– Enzymes, which speed up the rate of chemical reactions
within the body.
• Enzymes usually end with –ase, and are a necessary
component of every form of chemical change in the
body, such as the steps of the citric acid cycle.
• Proteins are made
of one or more
polypeptides, or
chains of amino
acids.
• Insulin, a protein
hormone that
helps regulate
blood sugar, is
made of two
polypeptides.
• Proteins form very
complex threedimensional structures
that are directly the
result of their primary
structure, or sequence
of amino acids in their
polypeptides.
– A change of even a
single amino acid can
alter the entire shape
of the protein.
DNA to Protein
• The nucleus is able to control the cell by directing
the amount and types of proteins produced by the
ribosomes in the cytoplasm and rough endoplasmic
reticulum.
– This entire process is called protein synthesis and
begins with the DNA that makes up the
chromatin/chromosomes in the nucleus.
DNA and RNA
• DNA and RNA are both nucleic acids; polymers of
nucleotides.
• Nucleotides are made of three units:
– A sugar (ribose or deoxyribose)
– A phosphate group (PO4)
– A nitrogenous base
• The sugar and phosphate
are part of the structure of
the DNA molecule, but
don’t play a direct role
in protein synthesis.
• There are four types of nitrogenous bases found in
nucleotides.
– The sequence of these bases determines the type of
protein that will be made from the DNA template.
• Each base is given an abbreviation.
–
–
–
–
A = Adenine
T = Thymine
C = Cytosine
G = Guanine
• The structure of the DNA molecule was first
observed by Rosalind Franklin, who used X-ray
crystallography.
• Two other scientists, James Watson and Francis
Crick, deduced that the nitrogenous bases were at
the center of the molecule, with the phosphate and
sugars making up the sides.
• The final piece of the puzzle was that adenine (A)
bonded best with thymine (T), and cytosine (C)
bonded best with guanine (G).
• DNA forms a double-helix shape, with two
spiraled polynucleotide strands bonded down the
middle.
DNA Replication
• During replication, the doublehelix will be untwisted and the
base pairs separated.
– This process is catalyzed by an
enzyme, DNA helicase.
• Each strand becomes a template
for the assembly of a new
complementary strand.
– This process is called the
semiconservative model of
replication, because each daughter
DNA molecule will actually have
one strand from the original
parent DNA molecule.
• The enzyme responsible for producing the new
DNA strand is DNA polymerase.
– DNA polymerase can only work on one direction –
from the end labeled 5’ (five-prime) to the end labeled
3’.
• DNA replication will begin at multiple sites, called
origins of replication and form “bubbles” that
gradually enlarge until the entire molecule is
synthesized.
• Following base-pair rules, what complementary
strand would be formed from this parent molecule?
Protein Synthesis
• Remember, each of the heritable traits in our bodies
are the result of genes, or specific segments of DNA.
• Eye color, for example, is the result of two or more
genes that collectively determine the amount of a
pigment protein called melanin produced in the irises
of the eyes.
Allele
Combination
Effect on Protein Color
Synthesis
BB GG
Lots of melanin
produced in the
irises of the eyes.
BB Gg
Bb GG
Dark brown
Medium
brown
Bb Gg
BB gg
bb GG
Bb gg
bb Gg
bb gg
Light brown
or hazel
Dark blue or
green
Little or no
Light blue
melanin produced.
One Gene, One Polypeptide
• Each gene transcribes for one polypeptide.
– Proteins may be made of one or more polypeptides.
• Polypeptides are produced in ribosomes, which are
in the cytoplasm.
• Chromatin is too large to easily exit nuclear pores,
so a “copy” of the gene is made from a singlestranded molecule of RNA.
– This process is called transcription.
• The overall process of protein synthesis can be
summarized as:
– DNA → RNA → Polypeptide
• Transcription
begins when an
enzyme, RNA
polymerase, binds
to a specific gene,
or segment of DNA
on a chromosome.
– The new
molecule, called
mRNA, is formed
based on the DNA
template.
• mRNA has a few important
structural differences, compared to
DNA:
– The sugar in the molecule’s
backbone is ribose instead of
deoxyribose.
– It is only single-stranded.
– The nitrogenous base uracil (U) is
used in place of thymine.
• RNA synthesis within transcription
follows this pattern:
–
–
–
–
A U
TA
CG
GC
• Nitrogenous bases are read
by RNA polymerase three
at a time, a unit called a
codon.
– Each codon will eventually
translate into a single
amino acid.
• The first codon in the
mRNA sequence is called a
promoter, or “start” codon.
– AUG
• Transcription continues
until one of the three
terminators, or “stop”
codons is reached.
– UAA
– UGA
– UAG
• The mRNA must next be used to generate the
required polypeptide in a ribosome.
– This stage is called translation.
• Each codon on the mRNA molecule is matched up
to a complementary anticodon, or group of three
bases on a tRNA molecule.
– For example, if the codon on the mRNA is CCG, the
anticodon on the tRNA will be GGC.
• tRNA carries
an amino acid,
which is added
to the chain of
the new protein.
• The genetic code is non-ambiguous, meaning that
each codon specifies for one amino acid.
– For example, AUU always codes for isoleucine.
• The genetic code is also redundant, meaning that each
amino acid may be coded by multiple codons.
– For example, isoleucine is coded by AUU, AUC, and AUA.
– Redundancy helps to avoid damage if an error occurs in
transcription.
Example: Insulin
• Insulin is a protein
hormone that
regulates blood sugar.
• The protein is made of
two polypeptide
chains joined by a
connecting peptide
and capped by a signal
peptide.
How Insulin is Built
1. The double helix of the
relevant section of
chromosome 11 is
unzipped by DNA
helicase.
2. The mRNA molecule is
transcribed by RNA
polymerase using one of
the DNA strands as a
template.
3. The mRNA molecule is
sent through a nuclear
pore to the rough
endoplasmic reticulum.
How Insulin is Built
4. The mRNA is received by a
ribosome in the rough E.R.,
which starts translating the
mRNA codons into amino
acids.
5. The protein is built, one
amino acid at a time, using
tRNA molecules.
6. The insulin is sent to the
Golgi, where it is packaged
before released through the
cell membrane.
Mutations
• Any change in the nucleotide sequence of DNA is
called a mutation.
• Substitution mutations occur when the wrong
nucleotide is inserted during DNA replication.
– Example: A thymine (T) is inserted instead of an
adenine (A) in a complementary DNA strand.
• Insertion mutations occur when an extra
nucleotide is inserted into the complementary DNA
strand.
• Deletion mutations occur when a nucleotide is
skipped and not added to the complementary DNA
strand.
Substitution Mutations
• If a substitution mutation does not affect the
primary structure of the polypeptide, it is called a
silent mutation.
• A missense mutation results in the insertion of a
single incorrect amino acid in the poly peptide.
• Sickle-cell anemia is the result a missense mutation
in the gene that codes for one of the four
polypeptides of the hemoglobin protein in red
blood cells.
Substitution Mutations
• A nonsense mutation changes an amino acid codon
to a stop codon, prematurely terminating the
protein.
– This is the most damaging of the substitution
mutations.
Frameshift Mutations
• Insertions and
deletions are also
called frameshift
mutations because
they completely
disrupt the reading
frame, or triplet
grouping of the gene.
– Nearly every amino
acid following the
mutation will be
incorrect, completely
altering the structure
of the protein.
Mutagens
• Mutations can occur spontaneously during DNA
replication or can be the result of physical or
chemical agents called mutagens.
– Examples include ultraviolet radiation, X-rays,
asbestos, and tobacco smoke.