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Interaction of GAPR-1 with lipid bilayers is regulated by alternative homodimerization

2012; Elsevier BV; Volume: 1818; Issue: 9 Linguagem: Inglês

10.1016/j.bbamem.2012.04.016

1879-2642

Josse van Galen, Nick K. Olrichs, Arie Schouten, Ramón Serrano, Esther N. M. Nolte‐‘t Hoen, Ruud Eerland, Dora V. Kaloyanova, Piet Gros, J. Bernd Helms,

Trace Elements in Health

Golgi-Associated Plant Pathogenesis-Related protein 1 (GAPR-1) is a mammalian protein that belongs to the superfamily of plant pathogenesis related proteins group 1 (PR-1). GAPR-1 is a peripheral membrane-binding protein that strongly associates with lipid-enriched microdomains at the cytosolic leaflet of Golgi membranes. Little is known about the mechanism of GAPR‐1 interaction with membranes. We previously suggested that dimerization plays a role in the function of GAPR‐1 and here we report that phytic acid (inositol hexakisphosphate) induces dimerization of GAPR‐1 in solution. Elucidation of the crystal structure of GAPR‐1 in the presence of phytic acid revealed that the GAPR‐1 dimer differs from the previously published GAPR‐1 dimer structure. In this structure, one of the monomeric subunits of the crystallographic dimer is rotated by 28.5°. To study the GAPR‐1 dimerization properties, we investigated the interaction with liposomes in a light scattering assay and by flow cytometry. In the presence of negatively charged lipids, GAPR‐1 caused a rapid and stable tethering of liposomes. [D81K]GAPR‐1, a mutant predicted to stabilize the IP6‐induced dimer conformation, also caused tethering of liposomes. [A68K]GAPR‐1 however, a mutant predicted to stabilize the non‐rotated dimer conformation, is capable of binding to liposomes but did not cause liposome tethering. Our combined data suggest that the charge properties of the lipid bilayer can regulate GAPR‐1 dynamics as a potential mechanism to modulate GAPR‐1 function.