Effects of phosphatidylethanolamine glycation on lipid-protein interactions and membrane protein thermal stability

VALERIA LEVI; ANA M VILLAMIL GIRALDO; PABLO R. CASTELLO; JUAN PABLO F.C. ROSSI; F. LUIS GONZÁLEZ FLECHA

BIOCHEMICAL JOURNAL

Portland Press

Lugar: Londres; Año: 2008 vol. 416 p. 145 - 152

0264-6021

Non-enzymic glycation of biomolecules has been implicated in the pathophysiology of aging and diabetes. Among the potential targets for glycation are biological membranes, characterized by a complex organization of lipids and proteins interacting and forming domains of different size and stability. In this work, we analyze the effects of glycation on the interactions between membrane proteins and lipids. The phospholipid affinity for the transmembrane surface of the plasma membrane calcium pump (PMCA) was determined after incubating the protein or the phospholipids with glucose. Results show that the affinity between PMCA and the surrounding phospholipids decreases significantly after phosphospholipid glycation, but remain unmodified after glycation of the protein. Further, phosphatidylethanolamine glycation decreases ~ 30 % the stability of PMCA against thermal denaturation, suggesting that glycated aminophospholipids induce a structural rearrangement in the protein that makes it more sensitive to thermal unfolding. We also verified that lipid glycation decreases the affinity of lipids for two other membrane proteins, suggesting that this effect might be common to membrane proteins. Extending these results to the in vivo situation, we can hypothesize that under hyperglycemic conditions glycation of membrane lipids may cause a significant change in the structure and stability of membrane proteins, which may affect the normal functioning of membranes and therefore of cells.