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Molecules and that > Apoptosis controlling overall and Bcl-2 > Flashcards

Apoptosis controlling overall and Bcl-2 Flashcards

1
Q

What is apoptosis dependent on?

A

CASPASES - A family of ProteASES that have a Cysteine at their active site and cleave their target proteins at specific ASpartic acids.

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2
Q

What do caspases do once active?

A

Activate other caspases - an amplifying proteolytic cascade

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3
Q

What is an amplifying proteolytic cascade?

A

Caspases activating other caspases

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4
Q

What are the 2 ways caspases are activated?

A

From OUTSIDE the cell by activation of death receptors on the cell surface or suicide.

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5
Q

What is the first step of the EXTRINSIC mechanism? The first stage.

A

Killer lymphocytes carrying Fas ligand binds and activates Fas proteins on the surface of target cells.

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6
Q

What is a Fas ligand?

A

Fas ligand s a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. Its binding with its receptor induces apoptosis.

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7
Q

What is the second step of the extrinsic mechanism?

A

Adaptor proteins bind to Fas proteins and cause aggregation of PRO-CASPASE-8 molecules.

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8
Q

What is the first stage of the INTRINSIC mechanism?

A

Mitochondria release cytochromc C, which binds and caused aggregation of Apaf-1

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9
Q

What is the second stage of the intrinsic mechanism?

A

Apaf-1 binds and aggregates procaspase-9 molecules

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10
Q

What is the third and final stage of both the extrinsic and intrinsic mechanism?

A

Procaspase cleaved, triggering caspase cascade.

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11
Q

What is BCL-2?

A

Bcl-2 family are promotors/suppresors of apoptosis; regulators.

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12
Q

What are caspases?

A

Cystine proteases, executioners of apop.

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13
Q

Which Bcl-2 family molecules are anti-apop?

A

Bcl-2 and Bcl-x

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14
Q

Which Bcl-2 family molecules are pro-apop?

A

Bax, Bak, Bid, Bim

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15
Q

Where do Bcl-2 family reside?

A

Mitochondrial membrane

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16
Q

What can pro-apop Bcl fam molecules stimulate?

A

They can stimulate release of cyt-c OR inactivate death-inihibiting members of the fam

17
Q

Which of the two, pro/anti apop members can be heterodimers?

A

Both

18
Q

How does Anti-apop block pro-apop’s activity?

A

Dimers with it

19
Q

What determines whether a cell will live or die?

A

Relative levels of pro/anti

20
Q

Describe the structure of Bcl-Xl

A

7 alpha helices in 3 layers - 2 central surrounded by amphipathic.

21
Q

Is Bcl-Xl an inhibitor or promoter of apop?

A

Inhbitor

22
Q

What does Bcl-Xl resemble?

A

Bacterial toxins - they have central alpha helices to penetrate membranes and form channels whereas Bcl-2 family forms pH dependent ion conducting channels.

23
Q

What kind of channels does the Bcl-2 family form?

A

pH-dependent ion conducting channels

24
Q

How does the Bcl-2 family regulate programmed cell death?

A

DIMERISATION

25
Q

What of the Bcl-2 family is functionally important?

A

4 homology regions - Bcl1, Bcl2, Bcl3, Bcl4. Bcl1-3 cluster on one side of the molecule and form a hydrophobic patch

26
Q

Which homology region(s) is required for Bak/Bax dimerisation?

A

BH3

27
Q

What does Bak bind to and via what kind of peptide?

A

Bcl-Xl via a 16 residue BH3 containing peptide as an alpha helix that fits into a hydrophobic cleft formed by residues in the BH1-3 regions of Bcl-Xl

28
Q

What form interactions play a part in dimerisation? And which form plays a part with the Bak BH3 helix?

A

Electrostatic AND hydrophobic. and hydrophobic residues of Bak BH3 helix that face the protein contribute to the complex formation. The Leu78 of Bak interacts extensively with Bcl-Xl

29
Q

What happens if the Leu of Bak mutates to an Al?

A

Binding affinity for Bcl-Xl reduces 800 fold. CANCER.

30
Q

What contributes to the specificity of the Bcl-Xl-Bak interaction?

A

Salt-bridges

31
Q

What mediates Bcl-2 proteins interaction with other proteins?

A

BH4

Molecules and that (12 decks)

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