Download Introduction to Biochemistry, Cell and Molecular Biology II Losiana

Introduction to Biochemistry,
Cell and Molecular Biology II
Losiana Nayak
Indian Statistical Institute
http://www.isical.ac.in/~losiana_t/
Molecular Biology
A field of science concerned with studying the
chemical structures and processes of biological
phenomena at the molecular level.
A branch of biology dealing with the ultimate
physicochemical organization of living matter
and especially with the molecular basis of
inheritance and protein synthesis.
Ref: http://www.britannica.com/
Cell: structural unit of life
A cell can be
distinguished
into a outer
membrane,
central
nucleus and
cytoplasm.
Cell membrane
nucleus
cytoplasm
Typical structure of a cell
Robert Hooke, an English
scientist, first
described cells in
1665.
Cell theory consists of
three basic points:
1. All living things are
made of cells.
2. The cell is the
smallest living thing
that can perform all
the functions of life.
3. All cells must come
from preexisting
cells.
An animal Cell
Plant cells
are different
from animal
cells. They
contain the
green
photosynthetic
pigment
chloroplast.
Growth
The answer is cell division, which is of
two types
1.
2.
Mitosis [Somatic division]
Meiosis [Genetic division/
Reductional division]
Functions of a cell?
Genetic control
Energy house
Support
Storage
Packaging
Transport
Central Dogma of molecular biology
Information Only Goes One Way
The central dogma states that once “information”
has passed into protein it cannot get out again.
The transfer of information from nucleic acid to
nucleic acid, or from nucleic acid to protein, may
be possible, but transfer from protein to protein,
or from protein to nucleic acid, is impossible.
Information means here the precise determination
of sequence, either of bases in the nucleic acid or
of amino acid residues in the protein.
Francis Crick, 1958
T
Packaging
G
A
C C
GA
DNA
Histone
octomer
T
C A G T
G T C A
Histone proteins
T
A
G
C
B DNA Helix
C
G
T
A
2 nm
T
Packaging
G
A
C C
GA
DNA
Histone
octomer
T
C A G T
G T C A
Histone proteins
T
A
G
C
B DNA Helix
C
G
T
A
2 nm
T
Packaging
G
A
C C
GA
DNA
11 nm
T
C A G T
G T C A
Histone
octomer
Histone proteins
T
A
C
B DNA Helix
C
G
T
Nucleosome
G
A
2 nm
Packaging DNA
Histone H1
A
G T
C A
T
A
G
C
C
G
T
A
Packaging DNA
Histone H1
A
G T
C A
T
A
G
C
C
G
T
A
Packaging DNA
“Beads on
a string”
A
G T
C A
11 nm
30 nm
T
A
G
C
C
G
Tight helical
fiber
Looped
200 nm Domains
A
T
Protein scaffold
Packaging DNA
Nucleosomes
11 nm
30 nm
T
G
Tight helical fiber
Metaphase
Chromosome
700 nm
200 nm Looped Domains
C
A
2 nm
B DNA Helix
Protein scaffold
A “Simple” Eukaryotic Gene
Transcription
Start Site
3’ Untranslated Region
5’ Untranslated Region
Introns
5’
Exon 1 Int. 1
Promoter/
Control Region
Exon 2
3’
Int. 2 Exon 3
Exons
RNA Transcript
Terminator
Sequence
Eukaryotic Gene Expression
Cytoplasm
DNA
Packaging
Nuclear
pores
Transcription
Transportation
Modification
RNA
Nucleus
G
AAAAAA
Export
e
som
bo
Ri
RNA
Processing
mRNA G
Degradation
Degradation etc.
AAAAAA
Translation
Stages of Transcription
„
1.
2.
3.
Transcription can be logically
divided into three distinct stages:
Initiation
Elongation
Termination
Transcription Initiation
„
„
„
„
Proteins called transcription factors bind
to the promoter region of a gene
If the appropriate transcription factors
are present, RNA polymerase binds to
form an initiation complex
RNA polymerase melts the DNA at the
transcription start site
Polymerization of RNA begins
Coding
(sense) strand
5’
3’
3’
5’
Template
(antisense) strand
Transcription
Coding
(sense) strand
5’
3’
3’
5’
RNA
Pol.
5’
RNA
Template
(antisense) strand
Transcription
Coding
(sense) strand
5’
3’
3’
5’
Template
(antisense) strand
5’
RNA
Pol.
Transcription Termination
There are two types of termination:
„
„
Rho dependent requires a protein called
Rho, that binds to and slides along the RNA
transcript. The terminator sequence slows
down the elongation complex, Rho catches
up and knocks it off the DNA
Rho independent termination depends on
both slowing down the elongation complex,
and an AT rich region that destabilizes the
elongation complex
Termination
(Rho Independent)
RNA
Pol.
RNA
Pol.
RNA
5’
RNA
Pol.
5’
RNA
5’
Terminator
Termination
(Rho Dependent)
Terminator
RNA
Pol.
RNA
5’
ρ
Help, rho
hit me!
ρ
5’
5’
RNA
RNA
Pol.
RNA
Pol.
ρ
Products of Transcription
Transcription produces three major RNA
products:
1.Ribosomal RNA (rRNA) - Several rRNAs are vital
constituents of ribosomes
2.Transfer RNA (tRNA) - The molecule that
physically couples nucleic acid codons with
specific amino acids
3.Messenger RNA (mRNA) - The nucleic acid
messenger that carries encoded information from
genes on DNA to the protein manufacturing
ribosomes
„
Requirements for Translation
„
„
„
„
„
„
Ribosomes - rRNA and Protiens
mRNA - Nucleotides
tRNA
Aminoacyl-tRNA Synthetase,
L Amino Acids
ATP - For energy
Ribosome Structure
Peptidyl-tRNA
binding site
Aminoacyl-tRNA
binding site
P
Exit site
A
E
Large
subunit
5’ GAG...C-AGGAGG-NNNNNNNNNN-AUG---NNN---NNN---NNN---NNN--mRNA
Small subunit
3’
Translation - Initiation
fMet
Large
subunit
E
P
A
UAC
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
Small mRNA
subunit
3’
Translation - Elongation
Polypeptide
Arg
Met
Phe
Leu
Ser
Aminoacyl tRNA
Gly
Ribosome
E
P
A
UCU
CCA
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
mRNA
3’
Translation - Elongation
Polypeptide
Met
Phe
Leu
Ser
Gly
Arg
Aminoacyl tRNA
Ribosome
E
P
A
CCA UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
mRNA
3’
Translation - Elongation
Polypeptide
Met
Phe
Leu
Ser
Gly
Arg
Ribosome
E
P
A
CCA UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
mRNA
3’
Translation - Elongation
Polypeptide
Met
Phe
Leu
Ala
Ser
Gly
Aminoacyl tRNA
Arg
Ribosome
E
P
A
CGA
CCA
UCU
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
mRNA
3’
Translation - Elongation
Polypeptide
Met
Phe
Leu
Ser
Gly
Arg
CA
C
Ribosome
E
Ala
P
A
UCU CGA
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA
mRNA
3’
Translation - Termination
Met
Phe
Leu
Ser
Gly
Polypeptide
Arg
Ala
Ribosome
Val
E
P
A
CGA
CGA
GCA...TAAAAAA
STOP
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT
mRNA
3’
Translation - Termination
Met
Phe
Leu
Ser
Gly
Polypeptide
Arg
Ala
CG
Val
CG
A
P
A
E
A
5’GAG...CU-AUG--UUC--CUU--AGU--GGU--AGA--GCU--GUA--UGA-AT GCA...TAAAAAA 3’
mRNA
STOP
Transcription And Translation
In Prokaryotes
5’
3’
3’
5’
RNA
Pol.
Ribosome
mRNA
5’
Ribosome
AN OVERVIEW OF
METABOLISM
CARBOHYDRATE METABOLISM
LIPID METABOLISM
PROTEIN METABOILSM
ENERGY METABOLISM
WHAT IS METABOLISM?
A Continuous gradual process of
biological systems that includes
both building and breaking of
macronutrients for the purpose of
growth, reproduction
and
senescence.
WHAT IT INCLUDES?
METABOLISM
ANABOLISM
CATABOLISM
GENESIS
LYSIS
FATS
POLYSACCHARIDES
PROTEINS
Fatty acids
Glucose
Aminoacids
Glycerol
Other Sugers
CO A
Acetyl Co A
ATP
ADP
e
O2
OXIDATIVE
PHOSPHORYLATION
CITRIC
ACID
CYCLE
2CO2
Signal transduction pathway?
„
„
„
Signal means any communication that encodes
a message
Signal Transduction involves conversion of a
signal from extracellular environment to
functional changes within the cell
A Signal transduction pathway is a series of
steps that enable signal transmission through
physical barriers like cell membrane, organelle
membrane and nuclear membrane
General process of a STP
„
„
„
Extracellular signal is present outside a cell:
typically a hormone, neurotransmitter or growth
factor
Signal binds to a receptor causing a change in
receptor conformation, thus transmitting a signal
to the interior of the cell
The signal precipitates many enzyme catalyzed
protein interactions, ultimately causing changes
in the cell’s functions (ex. glucose uptake, cell
division, transcription)
Reference
™
™
Biochemistry by Lubert Stryer
Cell and Molecular Biology by
De Roberties and De Roberties
Some Slides are taken from
Timothy G. Standish, Ph. D.