Fig. 3. Roles of C1Bδ loops in lipid binding.

a Polar backbone atoms and hydrophobic sidechains of DAG-interacting C1Bδ residues create a binding site whose properties are tailored to capture the amphiphilic DAG molecule. This is illustrated through the deconstruction of the “sn-1” binding mode into three tiers that accommodate the glycerol backbone (tier 1), the sn-1/2 ester groups (tier 2), and the acyl chain methylenes (tier 3). b Residue-specific lipid-to-protein PRE values of the amide protons, ¹H Γ₂, indicate that loop β34 is inserted deeper into the membrane than β12. The PRE value for Trp252 is that for the indole NHε group. Cross-peaks broadened beyond detection in paramagnetic bicelles are assigned an arbitrary value of 120 s⁻¹. His270 and Lys271 cross-peaks are exchange-broadened and therefore unsuitable for quantitative analysis (open circles). The PRE values were derived from ¹H_N transverse relaxation rate constants collected on a single sample in the absence (diamagnetic) and presence (paramagnetic) of 14-doxyl PC. The error was estimated using the r.m.s.d. of the base plane noise. The inset shows the top view of the “sn-1” mode C1Bδ-DAG complex color-coded according to the hydrophobicity.