Download MBBS Translation Lecture PPT

TRANSLATION


Translation--

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is a process in which a polypeptide is synthesized

according to the nucleotide sequence of m RNA.

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It is carried out by a translation complex comprising m RNA,

tRNA, ribosomes.

Occurs at the ribosome in the cytoplasm.

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Uses anticodon to the tRNA to bring an aminoacid to the

ribosomes.
PROTEIN SYNTHESIS.

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TRANSLATION.

Takes place in ribosomes.
tRNA brings aminoacid to ribosomes.
tRNA forms a complimentary message ? anticodon.

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The aminoacid is read.
Aminoacid sequence continue until reaching a STOP codon.
PROTEIN SYNTHESIS.
STEPS FOR PROTEIN SYNTHESIS.

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STARTS WITH DNA.

Transcribe to mRNA.

mRNA speccifies aminoacid sequence in polypeptide.

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Brought by tRNA to r RNA.

Is translated into protein.
GENETIC CODE.

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GENETIC CODE-

Genetic code is the language used to

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convert the sequence of nucleotides in mRNA into the
sequence of amino acids of a protein.

A codon is a combination of three consecutive nucleotides

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present on DNA or mRNA. Hence, it is commonly called a
triplet i.e. a codon is a triplet of nucleotides.

Three codons do not code for any amino acid and the signal

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the termination of protein synthesis. These are called
termination codons or stop codons. These are UAA, UGA and
UAG.
I

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AUG is used as the first or initiation codon in all the proteins

synthesized from mRNA. It codes for methionine. Therefore, each
newly synthesized polypeptide chain [nascent chain] has
methionine as the first amino acid. However, it may not be present

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in final fully functional mature protein because this amino acid may
be removed during processing and maturation of protein.

Codons on mRNA or DNA(from which mRNA is transcribed) are

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read from 5` to 3` direction by the anti-codon loop of the tRNA.


TRANSLATION.
TRANSLATION IS COMPLETED IN 4 MAJOR STEPS.

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Charging of tRNA.

Initiation.

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Elongation and translocation.

Termination.

Folding and processing.

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Transport.
ACTIVATION OF AMINOACID AND CHARGING OF TRNA.

Components required.

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20 aminoacid.

20 aminoacyl tRNA synthesis.

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ATP.

Mg+
INITIATION.

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Component required.

mRNA.

fmet-Trna/met-tRNA

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30s/50s ? 70s

40s/60s--80s

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GTP

Mg+

Initiation factor.IF-1,IF-2,and IF-3.

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ELONGATION AND TRANSLOCATION.

Component required.

Initiation complex.

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Aminoacyl tRNA.

Mg++

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Elongation factor.

Peptidyl transferase.
TERMINATION.

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Component required.

ATP.

Termination codon.

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Release factor, RF-1, RF-2,RF-3.
TRANSLATION.

INITIATION--

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several initiation factors , AMP, and GMP are required and occurs in

the following stages.

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ACTIVATION OF AMINO ACID

SPLITING OF RIBOSOMES

PREINITIATION COMPLEX FORMATION

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FORMATION OF 48S PRE-INITIATION COMPLEX

FORMATION OF FULLY ACTIVE 80S INITIATION COMPLEX.

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ELONGATION

TERMINATION

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TRANSLATION IN PROKARYOTES.

INITIATION--

The 70s ribosome dissociated to form 30s and

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50s subunits. A set of three proteins called initiation factor (IF-

1, IF-2, and IF-3 ) take part in initiation. Bacterial ribosome

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contain three specific sites that bind aminoacyl-t RNAs. They

are the A site(aminoacyl site), the P site(peptidyl site) and the E

site(exit site).

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Two initiation factor, IF-1 and IF-3, bind to the 30s ribosomal

subunit .The m RNA now bind to the 30s subunit in such a

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fashion that the initiating codon (AUG) comes in to the P site on

the ribosome. AUG is the codon for methionine which has two t

RNAs.

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ELONGATION.

ELONGATION?

similar to initiation , a set of three elongation factor

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( EF-1, EF-2, EF-3 ) participate in the elongation .

1) Binding of an incoming aminiacyl ?t RNA.

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2) peptide bond formation.

3) Translocation.
TRANSLATION.

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TERMINATION-

Elongation continues until last aminoacid is added as

coded by the m RNA. One of the three stop codons ?UAA, UAG,UGA occurs

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immediately after the codon for the last aminoacid .
TRANSLATION IN EUKARYOTES.

INITIATION-
DISSOCIATION OF RIBOSOME -- The 80s intact

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ribosome dissociate to its constituent subunits-40s and 60s. Two
initiation factor (elF-1 and elF-2 ) bind to 40s subunit and delays
its reassociation with the 60s subunit allowing the binding of
other initiation factors to the 40s subunit.

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FORMATION OF THE PREINITIATION COMPLEX-- The elongation

factor -2 (elF-2) binds GTP to form a binary complex which in
turn associates with t RNA (carrying methionine) to form ternary

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complex.

The ternary complex bind to the 40s ribosomal subunit to form

43s pre initiation complex.

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INITIATION.

REQUIREMENT--
Initiation factor.
AMP, GMP.

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Occurs in following stages---
ACTIVATION OF Amino acid--
First amino acid combined to AMP to

form aminoacyl adenylate which is then attached to the

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corresponding t RNA.

SPLITING OF RIBOSOMES----
Ribosomes split into a smaller 40-S

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subunits and 60-S subunit . eIF -3 and Eif -1a bind to 40S subunit

and eLF-6 bind to 60s subunit to stabilize them and prevent their re

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association.


PRE INITIATION COMPLEX.

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PRE INITIATION COMPLEX--

Methionine is the starting amino

acid , so activated methionine , that is t RNA met first binds eLF

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-2 and GTP to form the ternary complex. Then ternary complex

then bind to stablized 40S subunit to form the 43s pre

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initiation complex.

FORMATION OF 48S pre-initiation complex ?

Binding of mRNA

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to 43s pre-initiation complex leads to the formation of 48s pre-

initiation complex. This is mediated by eLF-3, eLF-4F.

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The 48s-pre-initiation complex then scans the mRNA in 5'-3'

direction for the initiation codon.
INITIATION COMPLEX.

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FORMATION OF FULLY ACTIVE 80S INITIATION COMPLEX-

eIF-5 fascilitate the binding of 60S

ribosomal subunit to pre-initiation complex to form 80S

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initiation complex. At this point ,met-t-RNA(initiator tRNA) is on
the P site of ribosome to start the elongation.
INITIATION COMPLEX.

FORMATION OF INITIATION COMLEX--

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Activated m RNA is then

transferred to the 43s pre initiation complex to form 48s
initiation complex. The 48s initiation complex bind to the 60s

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ribosomal subunit to form the 80s initiation complex.
ELONGATION.

ELONGATION--

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once the process of translation is initiated, the

polypeptide chain is expanded in length by the sequential
addition of aminoacids.

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Elongation is a cyclic process occurs in three steps.

1.Binding of amino acyl ?t RNA to the A site.

2.Peptide bond formation.

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3.Translocation.


TRANSLATION

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TERMINATION-----

After several cycles of elongation incorporating

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the required number of aminiacids one of the three stop
codons (UAA, UAG, UGA) appears in the A site. The stop codon
is not recognised by any specific t RNA but a releasing factor
(RF) recognises and binds to the stop codon.
INHIBITORS OF PROTEIN SYNTHESIS

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Several antibiotics selectively act on bacterial ribosomes and

other ribosomes and other translation components to inhibit
protein synthesis and kill them.

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MECHANISM OF ACTION OF ANTIBIOTICS.

TETRACYCLIN

INHIBIT BINDING AMINOACYL tRNA to

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A site.

STREPTOMYCIN

Bind to 30s ribosome.

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chloremphenicol

Inhibit peptidyl transferase.

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Erythromycin

Binds to 50s ribosomes.

tetracycline

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Blocking the a site on the ribosome.
CONTROL OF PROTEIN SYNTHESIS.

CONTROL OF PROTEIN SYNTHESIS-

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Control of protein synthesis

occurs at the stage of initiation at two levels.

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By eIF-2, preventing 43S PIC formation and

BY eIF-4F complex and preventing 48S PIC formation.
REGULATION.

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REGULATION BY eIF-2 -

eIF-2 is a trimeric protein having a, B

and y subunits. It is activated by phosphorylation of a- subunits

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by several kinases.

Phosphorylated a-subunits binds to eLF2B and inctivates it.

This prevents 43S PIC formation and stops translation.

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REGULATION.

REGULATION BY elF-4F

eIF-4F is inactive when bound by a protein (4E-BP).

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On phosphorylation of 4EBP 4E becomes free and takes

part in 4F complex formation.

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4F then binds to mRNA cap and ultimately leads to the

formation of 48S PLC.
PROTEIN FOLDING

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Nascent protein undergoes folding with the help of chapreons

to acquire an appropriate three dimensional structure to
become active.

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Protein that do not fold properly and become non functional,

are degraded . Some may aggregate to produce Prion disease.
POST ? TRANSLATIONAL MODIFICATION.

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most of the newly synthesised proteins are not functional.

After attaining a three ? dimensional structure by folding
mechanism, these proteins undergo several structural and
chemical alteration to become fully functional.

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COVALENT MODIFICATION.

PHOSPHORYLATION.----

Phosphorylation ? Dephosphorylation

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depending on cellular needs.This process is under the control of hormones

and is the major mechanism of enzyme regulation.

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HYDROXYLATION.---

collagen synthesised as procollagen undergoes

extensive post translational modification to form mature collagen.

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GLYCOSYLATION.--

many proteins contain extensive carbohydrate side

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chain.

CARBOXYLATION...

ACETYLATION....

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Most of the translational processing occurs in the endoplasmic reticulam

and Golgi complex.