Modulation of Gel Phase Model Membranes by Vitamin D-Related Proteins

Abstract

Severe vitamin D deficiency has long been linked to dysfunctions of the musculoskeletal system, and more recent studies have also associated vitamin D deficiency with other conditions, ranging from certain cancers to cardiovascular disease and diabetes. Vitamin D is a steroidal hormone that can be biosynthesized from 7-dehydrocholesterol by the action of UV light on skin (vitamin D3 only), or obtained from dietary sources (vitamins D3 and D2). Vitamins D3 and D2 are inactive precursor molecules that must be successively hydroxylated in the kidney and liver in order to become active. The vitamin D binding protein (DBP, GC-globulin) is responsible for transporting the lipophilic vitamin D throughout the body, and the vitamin D receptor (VDR) is the transcription factor that exerts the most well-established activities of vitamin D in the cell nucleus. Here, we present data based on synchrotron X-ray diffraction, 31P NMR and 2H NMR describing the effects of DBP and VDR in modulating the phase behavior of model membranes composed of DPPC, brain-sphingomyelin and cholesterol. Initial results suggest that DBP particularly interacts with the bilayers to reduce the gel-fluid lamellar phase transition and increase lipid mixing in ternary membranes, with the effect of VDR being somewhat less significant. These data have consequences for our understanding of how the action of soluble proteins that bind lipophilic, membrane-based molecules may alter bilayer structure and dynamics as they interact with the membrane surface to identify and extract their target.