Human 5-HT3A -- Gln 476

Species Original Mutated to Mutation
Human Gln 476

Ala

Q476A
Rat Equivalent His 475    
Mouse Equivalent His 481    

 

Ala478Gly, Ala478Val, Ala478Leu

A478G and A478V mutations, in the human 5-HT3A subunit, had little effect on [3H] granisetron binding, relative to the WT 5-HT3AR, when receptors were expressed in COS cells. By comparison the A478L mutation resulted in a large reduction in [3H] granisetron binding.

The A478L mutant also resulted in a decrease in surface labeling, relative to the WT 5-HT3AR.

Removal of residue 478 resulted in a reduction in [3H] granisetron binding.

 

Tyr477Ala

The Y477A mutation in the human 5-HT3A subunit, exhibited increased [3H]granisetron binding relative to WT 5-HT3AR, when receptors were expressed in COS cells.

The 5-HT3A Y477A mutant also exhibited increased surface labeling relative to WT 5-HT3AR.

In addition, when the Tyr at position 477 (in mutant Q476A) was mutated to Ala, the result was an increase in surface expression, relative to the WT 5-HT3AR.

Removal of residue 477 and 478 (from the WT 5-HT3AR) resulted in a decrease in [3H] granisetron binding and surface labeling (see Table).

 

Gln476Ala

The Q476A mutation in the human 5-HT3A subunit exhibited increased [3H] granisetron binding relative to WT-5-HT3A, when receptors were expressed in COS cells.

The 5-HT3A Q476A mutant also exhibited increased surface labeling relative to WT 5-HT3AR.

In addition, when the Glu at position 476 (in mutant Y477A) was mutated to Ala, the result was an increase in surface expression, relative to the WT 5-HT3AR.

Removal of residues 476,477 and 478 (in the WT 5-HT3AR) resulted in a decrease in [3H] granisetron binding and surface labeling (see Table).



Name Mutations Truncations Relative(to WT-3A) Radioligand Binding Relative (to WT-3A) Membrane Expression
h-5HT-3A Q-Y-A      
N-4TM-QYG
Q-Y-G
  - NC
N-4TM-QYV
Q-Y-V
  - NC
N-4TM-QYL
Q-Y-L
  --- --
         
N-4TM-AYA
A-Y-A
  ++++ ++
N-4TM-QAA
Q-A-A
  ++++ ++
         
N-4TM-AAA
A-A-A
  +++ ++
N-4TM-AA
A-A-X
  -- ---
N-4TM-A
A-X-X
  ---- ----
         
N-4TM
 
X-X-X
---- ---
N-4TM-Q
 
Q-X-X
---- --
N-4TM-QY
 
Q-Y-X
---- --
         
Slight Reduction
-
Slight Increase
+
NC= No change
Reduction
--
Increase
++  
Large Reduction
---
Large Increase
+++  
Very Large reduction
----
Very Large Increase
++++  

 

Butler AS , Lindesay SA , Dover TJ , Kennedy MD , Patchell VB , Levine BA , Hope AG , Barnes NM (2009). Importance of the C-terminus of the human 5-HT3A receptor subunit.Neuropharmacology.56(1):292-302.

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