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Proteomics
• Proteomics is the study of protein structure and function.
• An organism’s proteome is its entire set of proteins.
• Proteomics is much more complicated than genomics.
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Proteomics Versus Genomics
• Genomics tells us what kinds of proteins a given organism has the capacity for producing, but genomics tells us almost nothing about how those proteins function or when and in which cells those proteins are produced.
• Proteomics gives us a clearer picture of what roles the various proteins play in cells. Therefore, compared to genomics, proteomics allows us to better understand an organism.
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3
Four Levels of Protein Structure
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DNA
Signal
Gene
NUCLEUS
Chromatin modification
Chromatin
Gene availablefor transcription
Exon
Intron
Tail
RNA
Cap
RNA processing
Primary transcript
mRNA in nucleus
Transport to cytoplasm
mRNA in cytoplasm
Translation
CYTOPLASM
Degradationof mRNA
Protein processing
Polypeptide
Active protein
Cellular function
Transport to cellulardestination
Degradationof protein
Transcription
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Regulationof geneexpression
trpE gene
trpD gene
trpC gene
trpB gene
trpA gene
(b) Regulation of enzyme production
(a) Regulation of enzyme activity
Enzyme 1
Enzyme 2
Enzyme 3
Tryptophan
Precursor
Feedbackinhibition
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Polypeptide subunits that make upenzymes for tryptophan synthesis
(b) Tryptophan present, repressor active, operon off
Tryptophan(corepressor)
(a) Tryptophan absent, repressor inactive, operon on
No RNA made
Activerepressor
mRNA
Protein
DNA
DNA
mRNA 5
Protein Inactiverepressor
RNApolymerase
Regulatorygene
Promoter Promoter
trp operon
Genes of operon
OperatorStop codonStart codon
mRNA
trpA
5
3
trpR trpE trpD trpC trpB
ABCDE
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(b) Lactose present, repressor inactive, operon on
(a) Lactose absent, repressor active, operon off
mRNA
Protein
DNA
DNA
mRNA 5
ProteinActiverepressor
RNApolymerase
Regulatorygene
Promoter
Operator
mRNA5
3
Inactiverepressor
Allolactose(inducer)
5
3
NoRNAmade
RNApolymerase
Permease Transacetylase
lac operon
-Galactosidase
lacYlacZ lacAlacI
lacI lacZ
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Enhancer TATAbox
PromoterActivators
DNAGene
Distal controlelement
Group ofmediator proteins
DNA-bendingprotein
Generaltranscriptionfactors
RNApolymerase II
RNApolymerase II
Transcriptioninitiation complex RNA synthesis
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Controlelements
Enhancer
Availableactivators
Albumin gene
(b) Lens cell
Crystallin geneexpressed
Availableactivators
LENS CELLNUCLEUS
LIVER CELLNUCLEUS
Crystallin gene
Promoter
(a) Liver cell
Crystallin genenot expressed
Albumin geneexpressed
Albumin genenot expressed
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Post-translational Modifications
• Phosphorylation• Ubiquitination• Methylation• Acetylation• Glycosylation
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Local signaling
Target cell
Secretingcell
Secretoryvesicle
Local regulatordiffuses throughextracellular fluid
(a) Paracrine signaling (b) Synaptic signaling
Target cellis stimulated
Neurotransmitter diffuses across synapse
Electrical signalalong nerve celltriggers release ofneurotransmitter
Long-distance signaling
Endocrine cell Bloodvessel
Hormone travelsin bloodstreamto target cells
Targetcell
(c) Hormonal signaling
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EXTRACELLULARFLUID
Plasma membrane
CYTOPLASM
Receptor
Signalingmolecule
Relay molecules in a signal transduction pathway
Activationof cellularresponse
Reception Transduction Response1 2 3
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Signalingmolecule (ligand)
Ligand-binding site
Helix
TyrosinesTyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosinekinase proteins
CYTOPLASM
Signalingmolecule
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Dimer
Activated relayproteins
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
Cellularresponse 1
Cellularresponse 2
Inactiverelay proteins
Activated tyrosinekinase regions
Fully activated receptortyrosine kinase
6 6 ADPATP
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
P
P
P
P
P
P
1 2
3 4
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