Chapter 3 - Proteins

Question 1

Most common regulatory small molecule added to amino acids

Answer 1

Phosphate - phosphorylation

1/3 of 10,000 or more mammalian proteins are phosphorylated at some point in time.

Question 2

Three ways phosphorylation affects proteins

Answer 2

1) because phosphate groups carry two negative charges - can cause major conformational changes in protein structure by, for example, attracting a cluster of positively charged amino acids.
2) addition of a phosphate group can mask a binding site that otherwise holds two proteins together - disrupts protein-protein interaction.
3) attached phosphate can form part of a structure used for protein recognition. Binding sites of other proteins would recognize such structure.

Question 3

Reversible protein phosphorylation controls the…

Answer 3

Activity, structure and cellular localizations of both enzymes and other proteins in eukaryotic cells.

Question 4

Protein kinase catalyze what reaction?

Answer 4

Protein kinases catalyze protein phosphorylation

Question 5

What protein remove phosphates from proteins?

Answer 5

Protein phosphatase

Question 6

About how many amino acids are there on the average protein kinase?

Answer 6

290 amino acids

Question 7

What are the short amino acid inserted into loops with protein kinase for?

Answer 7

Helps in recognizing the specific protein to phosphorylate.

To bind to structures that localize it in specific regions of the cell.

Question 8

What sub family of protein kinase cause Sarcoma cancer when deregulates?

Answer 8

Src. family of protein kinases - first kind of tyrosine kinases found and strangely branched of to tyrosine kinase from an ancestral serine/threonine kinase

Question 9

What anchors src proteins and their relatives to the cytoplasmic face of the plasma membrane?

Answer 9

A short N-terminal region that becomes covalent let linked to a strongly hydrophobic fatty acid

Question 10

Turning on a src protein

Answer 10

Two specific things:

1. Removal of C-terminal phosphate
2. Binding of the SH3 domain by a specific binding protein

Question 11

Src family protein general domains

Answer 11

NH2 - SH3 - SH2 - kinase domaine - COOH (500 amino acids)

Question 12

GTP-binding proteins

Answer 12

Proteins regulated by binding to a GTP/GDP. Usually active with GTP form and inactive with GDP.

• known also as GTPase because hydrolyze GTP to GDP

Question 13

Ras protein important for

Answer 13

In cell signaling. It’s GTP-bound form, it is active and stimulates a cascade of protein phosphorylation.

Usually in inactive GDP form

Question 14

What inactivates GTP-binding proteins?

What activates?

Answer 14

1. GTPase-activating protein (GAP). Switches GTP to GDP.

2. guanine nucleotide exchange factor (GEF)

Question 15

Prominent functions of phosphate and what amino acid it binds to.

Answer 15

Ser, Thr, Tyr

Drives the assembly of a protein into larger complexes

Question 16

Prominent functions of methyl and what amino acid it binds to.

Answer 16

Lys

Helps create distinct regions in chromatin through forming either mono-, di-, or trimethyl lysine in histones

Question 17

Prominent functions of acetyl and what amino acid it binds to.

Answer 17

Lys

Helps activate genes in chromatin by modifying histones

Question 18

Prominent functions of palmityl group and what amino acid it binds to.

Answer 18

Cys

Drives protein association with membranes

Question 19

Prominent functions of N-acetylglucosamine and what amino acid it binds to.

Answer 19

Ser, Thr

Controls enzyme activity and gene expression in glucose and homeostasis

Question 20

Ubiquitin

Answer 20

Binds to Lys (48)

Monoubiquitin addition regulates the transport of membrane proteins in vesicles

Polyubiquitin chain targets protein for destruction

Question 21

Two forms of protein regulation

Answer 21

1. Reversible binding of other molecules with protein

2. Covalent addition of small molecules to one or many amino acids in a protein.

Question 22

Two major intracellular signaling mechanisms in eukaryotes

Answer 22

1. Signaling by phosphorylated protein

2. Signaling by GTP-binding protein

Question 23

How is ubiquitin activated?

Answer 23

Ubiquitin-activating enzyme (E1) uses ATP hydrolysis to attach ubiquitin to itself through a high energy covalent bond (thioester bond).

Question 24

Ubiquitination

Answer 24

After ubiquitin activated (attached to E1)

1. E1 binds to ubiquitin-conjugating enzyme (E2)
2. E2 is primed with ubiquitin (transferred from E1) and E1 released.
3. E2 binds to ubiquitin ligase (E3)
4. E2-E3 complex finds degradation signal on target protein and binds
5. First ubiquitin chain added
6. Cycles more rounds depending on purpose

Question 25

Monoubiquitylation

Answer 25

Histone regulation

Question 26

Multiubiquitylation

Answer 26

Endocytosis

Question 27

Polyubiquitylation

Answer 27

1. Lys48 - proteasomal degredation.

2. Lys63 - DNA repair

Question 28

SUMO

Answer 28

Proteins similar to ubiquitin

Question 29

Degrons

Answer 29

Degradation signals

Question 30

SCF ubiquitin ligase description

Answer 30

1. Adds polyubiquitin
2. C-shaped structure formed from five protein subunits
3. Largest subunit serves as scaffold on which the rest of the complex is built
4. At on end of C is E2
5. Other end is substrate binding arm (known as F-box protein).

Question 31

Rapid destruction

Answer 31

During certain cases, depending on degron, a rapid addition of multiple ubiquitin can be added. If not rapid degron, ubiquitin is added one at a time slowly

Question 32

Successful protein and evolution

Answer 32

1. Genetic information tends to duplicate to produce a family of related proteins.
2. Many different F-box proteins
3. Family of scaffold as well