KARs and structural basis of activation Flashcards

1
Q

Which are faster, AMPARs or KARs?

A

AMPARs (but not by much)

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2
Q

What are two key properties of KARs?

A

Receptor summation

G protein coupled receptor

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3
Q

What is the difference between primary and secondary units of KARs? Which are which?

A

Primary units can form an ion channel on their own
Secondary units need at least one primary unit to form a pore

GluK1-3 are primary
GluK4-5 are secondary

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4
Q

Why are GluK4-5 secondary units?

A

They are more stubborn

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5
Q

Tetramers with only primary subunits have a typically ____ affinity as opposed to secondary subunits which have a ___ affinity

A

Lower

Higher

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6
Q

What are the 2 auxiliary subunits for Kaianate receptors?

A

Neto1 and 2

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7
Q

Rank the 3 receptor types in terms of their promiscuity

A

AMPARs are extremely promiscuous
KARs are the happy medium
NMDARs are extremely strict

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8
Q

What is PSD99 and how is it relevant to Receptors?

A

It lies under the cell and acts as a scaffolding, with several PDZ sites

Proteins with a PDZ binding site can latch onto it

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9
Q

What does the surface expression of KAR-neto complexes depend on?

A

Glu1/2/3 subunits

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10
Q

Why are Neto subunits important for KARs?

A

They allow for signal summation

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11
Q

What do KAR function depend on?

A

Location in the brain (and neto)

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12
Q

What are the 3 things that KARs can increase or decrease?

A

Glutamate release
GABA release
Cell excitability

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13
Q

What is the key function of Kainate receptors?

A

Modulation of neuronal circuits

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14
Q

What percent of KARs are edited at the Q/R site?

A

40%-50%

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15
Q

What is a property of the AMPAR which explains its speed?

A

Huge protein, basically touches postsynaptic terminal so when glutamate releases it’s “right there”

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16
Q

Describe the action of closed, open, and desensitized states

A

Glutamate binds LBD, twists open the pore
Crunches down ATD, desensitizes channel
Glutamate unbinds and protein relaxes

17
Q

What happened when receptors were chemically crosslinked?

A

They became poor at opening

18
Q

How can you get an AMPAR to act like a KAR?

A

By introducing a cation to the cation binding pocket of iGluRs

19
Q

What mechanism explains the fast iGluR gating?

A

Kiss and Run

20
Q

What creates electrostatic interactions in the NMDAR?

A

The water exclusion zone

21
Q

Is the NMDAR LBD dimer interface identical to that of AMPARs or KARs?

A

No but there is some overlap

22
Q

Which amino acid is critical for the onset and maintenance of NMDAR channel activation? Which is critical for maintenance only?

A

Tyr535 for onset + maintenance

E530 just for maintenance

23
Q

What is the purpose of the Tyrosine in the hinge region underneath the dimer interface?

A

Locks the dimer interface in a stable, open conformation (like a foot in the door, explains NMDAR channel opening behaviour)

24
Q

Why are AMPARs and KARs structural basis of activation electrostatic vs the NMDAR?

A

They’re on a much faster timescale