Upload File

dna rna protein synthesis amino acids protein protein ... · protein synthesis amino acids. some...

  • Home
  • Documents
  • DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are
29
DNA RNA PROTEIN FUNCTION Protein degradation Protein synthesis AMINO ACIDS

Upload: others

Post on 27-Jun-2020

10 views

Category:

Documents


0 download

Report

TRANSCRIPT

Page 1: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

DNA

RNA

PROTEIN

FUNCTION

Protein degradation

Protein synthesisAMINO ACIDS

Page 2: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are
Page 3: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Some properties of intracellular protein degradation (1970).

• Abnormal proteins are rapidly eliminated.

• Normal proteins are selectively degraded at widely different rates.

• Levels of specific proteins in animal cells can be regulated by

changes in rates of synthesis or rates of degradation (Schimke,

1970).

Page 4: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Hershko & Tomkins JBC 1971

Page 5: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Ciechanover, Hod & Hershko, BBRC 1978

Page 6: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

APF-1 (ubiquitin)

Protein (µg) 1.5 3 7 PNAS 1980

Page 7: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

ATPlysozyme (µg)

- -+ + + + +0 0 5 10 25 5 5

125I-ubiquitin

125I-lysozyme

lysozyme- (Ub)n

Hershko et al., PNAS 1980

Page 8: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

PNAS 1980

Page 9: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

DUBDUBDUB

E2E2E2 ProteinProtein

E3E3

UbUb

UbUb

UbUb

UbUb UbUb

UbUb

UbUb

UbUb

UbUb

E2E2E2

E1E1E1

UbUb

E1E1E1

+ATP+ATP

UbUb

AMP+PPAMP+PPiiE1E1E1

E2E2E2

UbUb

++ ATPATP

ADP+PADP+Pii

ProteinProteindegradeddegraded

26S proteasome26S proteasome

UbUb

ProteinProtein

UCHUCHUCH

Page 10: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Hershko et al., JBC 1983

Page 11: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Substrate Yes No Yes No Yes Yes

E3α-125I-proteincross-link

125I-protein

Cytochrome c (yeast)

Cytochrome c (mammalian)

Lysozyme

Ribonuclease A (native)

Ribonuclease A (oxidized 1)

Ribonuclease A (oxidized 2)

DETECTION OF E3-SUBSTRATE BINDING BY CHEMICAL CROSS-LINKING

Free 125I-proteinsJBC 1986

Page 12: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are
Page 13: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are
Page 14: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are
Page 15: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

MBC 1995

Page 16: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Cyclosome/APC

MBC 1995

Page 17: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

UU

UU

UU

UU

Cdk1

Cyclin B

Cdk1

Cyclin B

Cdk1

~ ~~ ~ Cdc20

PP

InactiveCdk1

InactiveAPC/cyclosome

ActiveAPC/cyclosome

E1, E2-CATP, Ub(b)

ATP

(a)

Cyclinsynthesis

26SProteasome

ActiveCdk1

Phosphatase

(d)

Cyclindegraded

Pi

PP

Cdc20

Page 18: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

APC/Cinactive

APC/Cactive

APC/Cinactive

APC/C = Anaphase-PromotingComplex/Cyclosome

Page 19: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

G0/G1 TimeTime

Lev

elL

evel

S

p27Cyclin E Cyclin A

Skp2

p27Cyclin E

Cdk2

Cyclin E

Cdk2

Cyclin A

Cdk2

Cdk2 inactive Cdk2 activep27 degraded

Cks1

Page 20: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

NCB 1999

Page 21: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

NCB 1999

Page 22: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

The three binding sites of Cks1

Cdk binding(green)Anion binding

(blue)

Skp2 binding(red)

JBC 2002

Page 23: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

p27Cyclin E

Cdk2p27

Cyclin E

Cdk2

Cyclin E

Cdk2

Cdk2 inactive

p27-(Ub)n

P

p27Cyclin E

Cdk2

Skp1

SCF complex

P

Skp2 &Cks1

synthesis

Skp2Cks1

Cyclin Esynthesis

Cdk2 active

p27 degraded

Page 24: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Some roles of ubiquitin-mediated protein degradation.

• Control of cell division• Signal transduction• Regulation of gene expression• Responses to inflammation• Immune response• Embryonic development• Apoptosis• Circadian clocks

Page 25: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Some regulatory proteins degraded by the ubiquitin system.

Regulator Role ofdegradation

Examples

I Positive Limitation of duration

Cyclins (G1, S, M-phase); transcription factors (myc, fos…)

II Negative Initiation of process

Cdk inhibitors Anaphase inhibitorIκB transcriptional regulator

III Positive or negative

Activation by stabilization

p53 tumor suppressor; β-catenin

Type

Page 26: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

2000

Microbe hunters

Vitaminhunters

Enzyme hunters

Gene hunters

1900

Arthur Kornberg : For the Love of Enzymes (1989)

Page 27: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Technion lab (1971-present)

Dvora GanothHanna HellerEsther EytanSarah EliasClara SegalJudith Hershko

Former graduate studentsAaron CiechanoverYuval ReissValery SudakinShirly Lahavand many others…

Collaboration and helpIrwin A. RoseLeonard CohenJoan RudermanMichele Pagano

Present graduate studentsGil BornsteinDanielle Sitry-ShevahYakir Moshe

Page 28: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are
Page 29: DNA RNA Protein synthesis AMINO ACIDS PROTEIN Protein ... · Protein synthesis AMINO ACIDS. Some properties of intracellular protein degradation (1970). • Abnormal proteins are

Plant proteins in relation to human protein and amino acid ... protein in... · (essential) amino acids lysine. sulfur amino acids, threonine, and tryptophan, which is constant across

Protein & Amino Acids

Protein: chain of amino acids joined by peptide bonds Amino Acids: The Building Blocks of protein. Consist of: Central carbon bonded to hydrogen Amino

Proteins. Protein is made of amino acids Amino acids are the building blocks of protein- they are organic acids Contain nitrogen Each amino acid has side

PROTEIN METABOLISM: PROTEIN TURNOVER; GENERAL WAYS OF AMINO ACIDS METABOLISM

Protein and Amino Acids

WHAT IS PROTEIN?. ENERGY YIELDING NUTRIENT What is protein composed of? What is protein composed of? What are amino acids? What are amino acids? Proteins

Protein turnover . Catabolism of amino acids III

Protein turnover Catabolism of amino acids II

Example2: Building a protein from amino acids: Substrate: Amino acids Product: The protein

Hierarchy of Protein Structure 20 different amino acids: many combinations The order of amino acids: Protein sequence Primary Structure Conformation varies

Amino Acids & Protein. Amino Acids What are amino acids? Structure Classification Understand pK Peptides and Peptide bond Examples of related compounds

11-Amino Acids and Protein Metabolism

UTILIZATION OF AMINO ACIDS FROM PROTEIN

Chapter 6 protein and amino acids

Protein Structure & Properties of amino acids

PROTEIN METABOLISM Kadek Rachmawati. PROTEIN METABOLISM Protein Catabolism Amino Acids Metabolism Amino Acids Catabolism Amino Acids Biosynthesis

Biochemistry ii protein (metabolism of amino acids)

Protein Engineering with Non-Natural Amino Acids

Proteins and amino acids. Protein Facts Proteins: Polymers of Amino Acids Proteins are polymers of amino acids. They are molecules with diverse structures

© 2006 Thomson-Wadsworth Protein: Amino Acids. © 2006 Thomson-Wadsworth Amino Acids

Non protein amino acids

Protein structure. Amino acids Amino acids: R group properties

Protein: Amino Acids Chapter 6. Amino Acid “R”“R”

03 amino acids and protein

Amino Acids and Protein Structure

Part (3): Amino Acids & Protein Metabolism Lecture …. amino acid...Non-essential amino acids in humans Amino acids that can be synthesized in the body. Alanine Asparagine Aspartate

Amino Acids, Peptides, Protein Primary Structure

Protein: Amino Acids

Engineering Proteins EP2 Protein Synthesis. Amino Acids

PROTEIN. ONE PROTEIN= 20 AMINO ACIDS AKA BUILDING BLOCKS OF PROTEIN

Chemistry of amino acids and protein

Proteins. Building Blocks of Protein: Amino Acids All protein is composed of Amino Acids Amino Acids are Nitrogen bearing compounds that form the structural

Amino acids and protein

Amino Acids Generalchemhaven.org/che102/EP/Ch29_4x6_Print.pdf · • Complete (animal) vs. Incomplete (vegetable) protein. Amino Acids Structure. Amino Acid Structure: • Amide,