CONFORMATIONAL CONSTRAINTS ON THE HEADGROUP AND SN-2 CHAIN OF BILAYERDMPC FROM NMR DIPOLAR COUPLINGS

This paper presents new NMR constraints on the conformation of the hea dgroup, glycerol backbone, and sn-2 chain of 1,2-dimyristoyl-m-glycero -3-phosphatidylcholine (DMPC) in the liquid-crystalline bilayer. Using two-dimensional C-13-H-1 chemical shift correlation spectroscopy, we find significant dipolar couplings between the carboxyl carbon CO2 and the headgroup protons. This indicates that a conformation in which th e DMPC headgroup and the beginning of the sn-2 chain bend toward each other is significantly populated in the fluid bilayer. The predominanc e of this headgroup orientation can be further confirmed by P-31-C-13 dipolar couplings from the literature, which constrain the glycerol G2 -G3 torsion angle to be close to trans, excluding a significant presen ce of one of the two conformations found in the DMPC crystal. Combinin g and reexamining 20 known NMR couplings for the glycerol backbone and its adjacent segments of L(alpha)-DMPC, we find that several torsion angles and bond orientations in the core of the DMPC molecule are cons trained severely and must differ from those in the crystal structure. We propose a consistent molecular model for phosphocholine lipids in t he liquid-crystalline phase, with a rigid backbone in the core of the molecule, a bent-back headgroup, and increasing mobility toward the en ds of the acyl chains and the headgroup.