unit4q
Protein
modification
The
newly synthesized polypeptide is not a functional protein until it assumes its
mature conformation through a series of foldings.
There may be other modifications necessary for the new protein to function.
These steps are termed posttranslational modifications. Some
amino acids in the polypeptide may be modified through the addition of sugars,
lipids, phosphates, methyl groups, etc. The protein may require that two or
more polypeptide chains bind together (quaternary structure - http://www.emc.maricopa.edu/faculty/farabee/BIOBK/3_14d.jpg).
The polypeptide may require cleavage. Often the initial methionine
is not found in a mature protein because it has been cleaved after translation.
Co-factors or co-enzymes are another type of modifications seen in proteins.
Many of these modifications occur in the Golgi
apparatus.
Here’s
a really good site with lots of pictures http://www.ksi.edu/demo/524/lecture.htm
Polypeptides
that require modification are translated on ribosomes
bound to the ER. A signal sequence on the mRNA directs the ribosome to dock on
the outside of the ER and the polypeptide enters the lumen of the ER as it’s
being translated. Proteins that are
destined to be included in the endomembrane system
(nuclear envelope, ER, Golgi, lysosomes,
etc) or the plasma membrane, and those destined to be exported from the cell
will carry a signal sequence on their mRNA. Proteins that function in the cytoplasm (e.g. glycolytic enzymes) will be translated on free ribosomes.
Mutations
DNA-DNA
replication is relatively error-free, but when a mistake occurs in a coding
message (point mutations), the resulting change could have adverse effects. It
is possible as well for this error to be transmitted to offspring. Mutations in the DNA can be classified as
base pair substitutions or insertions/deletions. We will consider only those mutations that
will affect the reading of the mature mRNA transcript.
SUBSTITUTIONS
A
substitution is the replacement of a C-G base pair with an A-T base pair or
vice versa.
Silent mutation: no change in the amino
acid sequence.
For example, changing CCG to CCA in the DNA will change the mRNA from GGC to
GGU. What follows? A glycine will be incorporated
into the polypeptide in either case. There is no change in the protein.
Missense mutation: a different amino acid is incorporated into the polypeptide
due to a change in mRNA codon. For example, in the
gene for hemoglobin, the codon GAA codes for
glutamate in position #6. A base pair
substitution changes the normal codon GAA to GUA. GUA
codes for valine which substitutes for glutamate at
that position. This substitution is the basis of sickle-cell anemia.
Nonsense mutation: an amino acid codon is changed to a termination codon.
When this happens, translation is likely to stop prematurely, leading to the
synthesis of a non-functioning protein.
INSERTIONS/DELETIONS
This
category includes the addition/loss of one or more base pairs. Because the
reading frame is altered (insertions/deletions are also known as frameshift mutations), the effects are more serious than
substitutions. If the mutation occurs near the end of the message, its effect
may be minimal.
For
an example see http://www.people.virginia.edu/~rjh9u/hbmutfs.html
READING FRAME
The
role of the ribosome is to serve as a workbench and to maintain the correct
reading frame of the mRNA. Messenger RNA is read in codons
of three nucleotide bases – like a language that consists of three-letter words
only.
Example:
THE
CAT
BIT THE DOG
an addition of one letter
TJH ECA TBI
TTH
the loss of one letter
TEC ATB ITT HED OG
An
addition or loss of three letter may restore the reading frame, but may alter
the meaning
THE FAT CAT BIT THE DOG
