Table 2 Summary of present results on disease mutants and comparison with previous studies.

From: Disease mutations reveal residues critical to the interaction of P4-ATPases with lipid substrates

 

Present study (bATP8A2, PS)a

Ref. 8 (ATP8B1, PC)b

Ref. 21 (Dnf2, PC)c

Mutant

I91P

L308F

E897K

L127P

I344F

E981K

L264P

N601F

E1261K

Expression

↓

WT

↓

↓

WT

n.d.

WT

WT

WT

Vmax

↓

WT

↓

Lipid uptake ↓

Lipid uptake ↓

WT

WT

↓

Apparent affinity for lipid

↓

↓

↑

WT

↓

↑

  1. The mutational effects indicated refer to measurements of ATPase activity stimulated by PSa or uptake of fluorescently labelled PC (substrate of ATP8B1 and Dnf2) in mammalianb or yeastc cells. A ≥1.5-fold change is considered different from wild type and is indicated by arrow pointing upward/downward for increase/decrease (WT = wild type-like). L127P, I344F, and E981K are disease mutations in ATP8B1 identified in patients. The equivalent mutations in the bATP8A2 studied here are I91P, L308F, and E897K, and in yeast Dnf2 L264P, N601F, and E1261K, respectively. Only a single PC concentration was tested with ATP8B1, thus precluding distinction between effects on Vmax and K0.5 b, and E981K was not studied (n.d., not determined)8. In the latter study, the lipid uptake was corrected for variation of ATP8B1 protein expression at the surface of the cells, thus being comparable to the Vmax value of the present study, which is the rate of ATP hydrolysis per mg of bATP8A2 protein.
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