Membrane Fusion Flashcards

1
Q

Eukaryotic cells are composed from

A

many membrane bound compartments

(such as nucleus, endosomes, lysosomes, mitochondria) that are designed to perform very specialized cellular functions.

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2
Q

cells need to have a mechanism that allows the transport of proteins in and out of these structures without _______. This is achieved via

A

compromising their identity.

intracellular vesicle transport

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3
Q

All cellular membranes are composed from a lipid

bilayer with charged residues facing the _____ and interacting with _____

A

outside

water molecules.

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4
Q

the membrane fusion thermodynamically is

A

highly inefficient event, since it needs to overcome the repulsive ionic forces and dissipate the hydration between to lipid bilayers.

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5
Q

cell need to have the machinery that increases the _____. In addition, cell needs to ensure the _______.

A

efficiency of membrane fusion

specificity of membrane fusion to ensure that the vesicular cargo is delivered to the correct destination

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6
Q

transport vesicle fusion steps.

A
  1. delivered to fusion site

2. fuse with the target membrane.

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7
Q

There are three main classes of SNAREs:

A
  1. syntaxins,
  2. VAMPs
  3. SNAPs
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8
Q

VAMP is located in _______ while syntaxin and SNAP are located in the _______.

A

transport vesicle,

target membrane

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9
Q

what drives membrane fusion?

A

The formation of highly stable SNARE complex

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10
Q

Once the fusion occurred, cell needs to ________.

A

recycle the SNARE proteins for another fusion events

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11
Q

Because the SNARE complexes are highly stable, ___ and ___ are required to disassemble

A
  1. NSF (N-ethyl-maleimide sensitive fusion protein)

2. αSNAP (soluble NSF attachment protein)

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12
Q

why are proteins required to disassemble SNARE?

A

because it is so stable

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13
Q

αSNAP stands for

A

soluble NSF attachment protein

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14
Q

NSF stands for

A

N-ethyl-maleimide sensitive fusion protein

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15
Q

The NSF uses _______ to generate energy needed to disassemble the SNARE complex.

A

ATP hydrolysis

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16
Q

After disassembly of SNARE complex, the SNARE proteins need to be _________.

A

refolded to the active conformation

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17
Q

Refolding of SNARE into active conformation is achieved by the ________

A

Sec1 protein

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18
Q

The class of enveloped viruses (includes _______) also needs to go through _____ in order to infect cells.

A

HIV, ebola, influenza viruses

membrane fusion

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19
Q

Viruses have developed _____

A

fusion machinery that is remarkably similar to SNARE fusion.

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20
Q

Normally, fusion domain is _______ within viral protein.

A

folded and hidden

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21
Q

Upon receiving specific signal (in case of influenza virus it is _____), the fusion domain is ________.
That is immediately followed by _____, leading to the ________.

A

change in pH

exposed and inserted into target cell membrane

refolding of fusion protein

fusion of viral and cellular membranes

22
Q

Sub-cellular protein targeting is important in ________.

A

delivering proteins required for specialized functions to different compartments within the cell.

23
Q

Cells must have a mechanism to transport proteins between these compartments without________

A

compromising the structure of the organelles or their membranes.

24
Q

Why do Cells and viruses require specialized machinery for membrane fusion?

A

Because membrane fusion is a thermodynamically unfavorable process due to repulsive ionic forces between the membranes and the presence of a layer of water coating the surfaces of membranes.

25
Q

SNARE proteins are

A

cellular proteins that aid in membrane fusion

26
Q

3 SNARE classes vary in structure but have one important commonality:

A

the presence of at least 1 alpha helical domain, which forms coiled coils

27
Q

When the alpha helical domains of SNARE proteins come into contact, they ______

A

zipper togther and form a highly stable complex of coiled coils

28
Q

the zippering of SNARE protein bridges the two membranes and allows

A

membrane fusion

29
Q

Because the helical complex between the SNARE proteins in highly stable,

A

the repulsive forces between the membranes are overcome and water molecules between the membranes are forced out

30
Q

Disassembly of SNARE protein complex is accomplished with a

A

“barrel-like” structured protein called NSF

31
Q

NSF contains

A

a catalytic protein called a-SNAP

32
Q

Once bound the SNARE complex, NSF function

A

twists to unwind the SNARE complex, hydrolyzing 6 molecules of the ATP process

33
Q

After the SNARE complex is disassembled, what happens to syntax in?

A

syntaxin folds onto itself and becomes inactive.

34
Q

how is syntax in reactivated?

A

n-Sec1 protein binds and refolds syntaxin to it’s active conformation

35
Q

How is the membrane fusion specificity achieved?

A

variations in the structure of the SNARE proteins.

36
Q

Because there are many variations in the structure of VAMPs, SNAPs and syntax in, this allows for the vesicles to fuse with _____, meaning that _____

A

vesicles to fuse with the appropriate membranes.

Only certain variants can match and associate with each other.

37
Q

Enveloped viruses have membrane that is derived from the _____

A

host cell

38
Q

enveloped viruses have _____ proteins

A

homotrimers of ciral fusion proteins

39
Q

domains that each viral fusion protein has: (3)

A
  1. transmembrane
  2. helical
  3. hydrophobic fusion
40
Q

the viral vision proteins of an inactive virus are folded to hide the _____ domain

A

hydrophobic fusion

41
Q

When the virus receives a certain signal, the protein stretches out and the fusion domain is exposed and inserted into the cell membrane.
Then the fusion membrane does what?

A

Then the fusion membrane ten folds back into a coiled coil, alpha-helical complex to bring the membrane in close proximity and allow for fusion

42
Q

______ signals for fusion domain in the influenza virus

A

low pH.

43
Q

With HIV, signaling for ______ occur in the same step

A

fusion domain exposure and membrane recognition

44
Q

____ is the viral fusion protein for HIV

A

Gp41

45
Q

In the HIV virus inactive stage, ____ binds to and blocks gp41 from _______

A

gp120

inserting into membrane

46
Q

When CD4 antigen on the membrane of a T cell binds to gp120. Then, what happens to gp120?

A

gp120 undergoes a conformational change that allows for both exposure of sites that bind to a receptor on the T cell membrane surface and exposure of the gp41 fusion domain.

47
Q

delivery to fusion site is helped by

A

molecular motor proteins that move along actin or microtubule tracks.

48
Q

Fusion with target membrane requires:

A

SNAREs (soluble NSF attachment protein receptor).

49
Q

Sec1 protein binds and changes _____ into ____ conformation.

A

syntaxin

active

50
Q

At low pH, the virus is able to

A

fuse with the endosome membranes in the cell

51
Q

The gp41 fusion domain then inserts into the target membrane. After insertion, the gp41 then does what?

A

refolds to bring the viral and target membrane into contact, gp120 dissociates and membrane fusion occurs