DETERMINATION OF HELIX-HELIX INTERACTIONS IN MEMBRANES BY ROTATIONAL RESONANCE NMR

Dimerization of human glycophorin A in erythrocyte membranes is mediated by specific interactions within the helical transmembrane domain of the protein. Rotational resonance NMR provides a unique approach for obtaining high-resolution structural data in membrane systems and has been used to establish intermolecular contacts in the glycophorin A dimer by using hydrophobic peptides that correspond to the transmembrane sequence. Magnetization exchange rates were measured between [C-13]methyl labels in the hydrophobic sequence -G(79)-V-80-M(81)-A(82)-G(83)-V-84- located in the middle of the transmembrane domain and specific [C-13]carbonyl labels along the peptide backbone across the dimer interface. Significant magnetization exchange was observed only between V-80 ((CH3)-C-13) and G(79) (C-13=O) and between V-84 ((CH3)-C-13) and G(83) (C-13=O), indicating that these residues are packed in the dimer interface in a ''ridges-in-grooves'' arrangement.