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The _____ _____ is the covalent bond between amino acids in a _______
peptide bond ; polypeptide
where does the peptide bond form between polypeptides?
It forms between the carboxyl end of an amino acid and the amino end of the next.
Many proteins consist of a
single polypeptide
Calmodulin is present in all _______ cells.
eukaryotic
what is calmodulin
a small protein that consists of a single polypeptide
what structure does calmodulin have
teritiary structure
calmodulin has _____ helices
alpha helices, a type of secondary structure observed in many proteins.
hemoglobin is an example of what
a protein with multiple polypeptides
Hemoglobin (Hb) is
the protein inside red blood cells that carries oxygen in the bloodstream
what is hemoglobulin made of
The complete protein has four polypeptides, two α-globins and two β-globins, and therefore has a quaternary structure.
Polypeptide:
a sequence of amino acids (1ry structure)
Alpha helix:
partial folding (2ry structure)
Globin:
complete folded polypeptide (3ry structure)
Hemoglobin:
four globins (4ry structure)
In sickle-cell anemia, a single amino acid substitution in
_______ reduces the affinity of Hb for ___ and impairing
the solubility and absorption of oxygen.
β-globin ; O2
in sickle cell anemia, The polypeptide forms large polymers that
distort the shape of red blood cells, affecting blood flow and oxygen transport.
Codon:
a three-base (nucleotides) sequence of DNA (a triplet) that codes for an amino acid.
start codon:
AUG, which also codes for methionine
stop codons:
UAA, UAG, and UGA (these do not code for
any amino acids)
the genetic code is expressed as
mRNAs in the 5’ => 3’ orientation
Characteristics of the genetic code
Unambiguous:
each of the 61 triplets code for only one of
the 20 amino acids.
Characteristics of the genetic code
Degenerate:
most amino acids are encoded by more than
one codon.
Characteristics of the genetic code
Universal:
most living organisms use the same code, but
exceptions exist.
Characteristics of the genetic code
Commaless:
there are no breaks between the codons in a reading frame (all the bases of the translated sequences are part of codons).
Characteristics of the genetic code
Non-overlapping:
the triplets in a reading frame are in a tandem sequence and do not overlap.
Spontaneous mutations can also result in ______ changes
permanent
Spontaneous mutations are or are not caused by errors in DNA replication?
are not
DNA exists inside of the cell, which is an ___ system.
open
DNA is exposed to _____ and _____ that can react with it and cause chemical alterations.
radiations and molecules
When a base is ______ by a different base in DNA, the result is a permanent ____ ____ ____
replaced ; single codon change.
Silent:
the resulting new codon codes for the same amino acid as the original codon.
Missense:
the new codon codes for a different amino acid.
Nonsense:
the new codon is a stop codon, resulting in a shorter polypeptide.
mutations may also be caused by
errors in DNA replication
mutations occur in the ___ and may be copied to ____
DNA ; mRNAs
what are also due to errors in DNA replication
insertions
All the codons from the insertion site on are changed, resulting in a
frameshift
The _____ of single bases by errors in DNA replication also occur and also result in frameshift mutations.
deletions
what type of disease is Huntington's disease
neurodegenerative
describe huntingtons disease
It is an autosomal dominant disease
caused by the expansion of trinucleotide CAG repeats, which code for glutamine in the mRNA, in the huntintin gene resulting in polyglutamine Huntingtin proteins.
Basic requirements of translation
mRNA
charged transfer RNAs (tRNAs)
ribosome
other requirements: initiation factors, elongation factors, and energy sources
no primers of any kind
An amino acid is attached to the
3’ end of the tRNA.
The ______ loop base-pairs with a codon in an ______.
anticodon ; mRNA
Inosine is a
modified adenine.
The post-transcriptional modification of bases in tRNAs result in
unusual bases.
what is the wobble hypothesis
The interaction between the third position of the codon in the mRNA and the first position of the anticodon in the tRNA is less critical and less constrained.
•some tRNA bases can pair with multiple mRNA bases at this position
•this allows translation to occur without the need for the cell to synthesize all 61 tRNAs
•inosine is a post-transcriptionally modified adenine that can occur at the wobble site of tRNAs
Charging:
the carboxyl group of the amino acid is covalently attached to the 3’ end of a tRNA.
Charging is catalyzed by twenty different Aminoacyl tRNA
twenty different Aminoacyl tRNA synthases
Energy is spent in charging in order to eventually make a
new ____ ____ in the ribosome.
peptide bond
charging step 1
amino acid activation:
the amino acid (AA) is converted to an aminoacyladenylic acid (AA-AMP).
This is the energy-consuming step in the process of
eventually making a new peptide bond. It requires ATP
charging step 2
the aminoacyladenylic acid loses the AMP and the carboxyl group of the amino acid is attached to the 3’ end of a tRNA.
The result is an aminoacyl tRNA (a charged tRNA).
Ribosome:
large particle of rRNA and proteins where translation occurs
two subunits: small and large
The Svedberg unit (S) is not a measure of molecular weight,
but a measure of
the rate at which particles sediment in a
centrifugal field.
the rate of svedberg unit depends on
weight, shape, and size.
Svedberg values
(for prokaryotic ribosomes):
•small subunit: 30S
•large subunit: 50S
•complete ribosome: 70S
Steps in the initiation of translation:
mRNA binds to the small ribosomal subunit with
the AUG codon positioned on the P site.
f-Met-tRNA (in prokaryotes) binds to the AUG codon.
The large ribosomal subunit joins the complex.
This process requires GTP for a source of energy plus a
series of initiation factors (IF proteins).
EF-Tu (an elongation factor) and GTP facilitate the binding
of the ____ _____ to the second codon at the __ site
second tRNA ; A
the amino acid on the first tRNA is transferred and forms
a _____ ____ with the amino acid on the second tRNA
(a _____ forms); the first tRNA moves to the E site
peptide bond ; dipeptide
the mRNA is shifted to place the second codon in the __ site
and to bring the third codon into the __ site
P ; A
the tRNA carrying the third amino acid binds the third codon on the _ site
A
the dipeptide on the second tRNA is transferred to form a
_____ attached to the third tRNA; the second tRNA
moves to the E site with the help of EF-G and GTP
tripeptide
Termination of translation
step 1:
A STOP codon moves to the A site of the ribosome. No tRNAs bind to stop codons.
Termination of translation
step 2:
Release factor 1 (RF1) binds to the stop codon
Termination of translation
step 3:
the GTP-dependent Release factor 3 (RF3) releases the
polypeptide chain from the last tRNA and the entire
translation complex dissociates
The diphtheria toxin inhibits
the last step of the polypeptide elongation cycle
The diphtheria toxin is produced by
Corynebacterium diphtheriae.
inhibits the eukaryotic elongation
factor 2 (EF2), which is analogous to the prokaryotic EF-G.
Translation is blocked and no new proteins can be made.