Influence of the 524-VAAEIL-529 sequence of annexins A6 in their interfacial behavior and interaction with lipid monolayers.

Annexin A6 (AnxA6), a calcium- and membrane-binding protein, is expressed in
mammalian cells in two isoforms: AnxA6-1 and AnxA6-2, the latter lacking the 524-
VAAEIL-529 sequence at the start of repeat 7. The different intracellular localization of
these two isoforms suggests distinct function in membrane dynamics. The aim of this
work was to analyze the behavior of AnxA6 isoforms at the air/water interface alone and
in the presence of membrane mimicking lipid monolayers. Using Langmuir technique
showed that AnxA6-2 was less adsorbed to the neat air-water interface than AnxA6-1 at
acidic pH and minor differences in their PM-IRRAS spectra were observed. Both
isoforms exhibited similar behavior towards cholesterol monolayer. However, the
interactions of AnxA6-2 with cholesterol ester monolayer were most favorable compared
to AnxA6-1. Our experimental data are discussed in relation with the different
intracellular localization of the two isoforms and with our constructed model of AnxA6-2
with the known crystal structure of AnxA6-1 showing the persistence of the 516-529 α-
helix in AnxA6-2 despite the absence of the 524-VAAEIL-529 sequence.