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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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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