Research News

Recently, Gianluigi Veglia and his research group published a hot paper in Biochemistry characterizing the structural dynamics and topology of phospholamban (PLN) in oriented lipid bilayers using solid-state nuclear magnetic resonance spectroscopy [Traaseth et al. 2006, Biochemistry 45, 13827-34].

PLN is a single-pass transmembrane protein that regulates heart muscle contraction and relaxation by reversible inhibition of Ca-ATPase, a large membrane enzyme responsible for Ca²⁺ flow into the sarcoplasmic reticulum. In this paper, two-dimensional PISEMA (an experiment correlating ¹H-¹⁵N dipolar coupling with the anisotropic ¹⁵N chemical shift) carried out in DOPC/DOPE mixed lipid bilayers fully reveal the tilt and rotation angles of the transmembrane and cytoplasmic domains of PLN with respect to the membrane bilayer normal. Additionally, the research also revealed dynamic information. Specifically, PLN undergoes fast long-axial rotational diffusion about the bilayer normal with the cytoplasmic domain undergoing this motion and other complex dynamics. While some of this dynamics was revealed by previous solution nuclear magnetic resonance relaxation studies in detergent micelles, these measurements in anisotropic native lipid environment reveal new dynamic features encoded in the free protein that might be crucial for Ca-ATPase recognition and the inhibitory mechanism.