Membrane-bound desaturases

Figure 1: SCD, shown as a red cartoon with pink surface, is situated in the membrane, shown in magenta lines with phosphates as beads, with the stearoyl-CoA substrate in yellow and surrounding water in cyan.

How is the diversity of lipids the body requires created through the action of membrane-bound desaturases?

Lipids have numerous roles in the body beyond the storage of fats, including contributing to membrane protein function, participating in cell signalling, and influencing synaptic activity in neurons, among many other roles. This range of lipid products with important roles in the body is in part due to the action of membrane proteins that desaturate the lipid between particular carbons, resulting in a lipid product with a new double bond. Through the action of membrane-bound desaturases, a diversity of lipid products that vary in number and placement of double bonds is created. Characterization of these membrane-bound desaturases is particularly well-suited to computational investigation because many rely on molecular oxygen and nonpolar substrates, making them difficult to explore through crystallization or wet lab methods alone.

For example, stearoyl-CoA desaturase (SCD) is an important metabolic control point in lipid metabolism (Figure 1). It introduces the first desaturation to the fully saturated lipid. Characterization of this protein's action through computational investigation will further efforts to understand how the desaturation occurs and how it can be manipulated.

This project is a collaborative effort with Dr. Joseph Ng's Lab at the University of Alabama in Huntsville and Dr. Ryan Yates' Lab at the University of Mississippi.