Molten globule state of tear lipocalin: ANS binding restores tertiary interactions

Tear lipocalin (TL) may stabilize the lipid layer of tears through a molten globule state triggered by low pH. EPR spectroscopy with site-directed spin labeling, revealed the side chain mobility of residues on the G-strand of TL in a molten globule state; the G-strand retains β-sheet structure. All of the side chains of G-strand residues become more loosely packed, especially residues 96-99. In contrast, the highly mobile side chain of residue 95 on the F-G loop, becomes tightly packed. ANS binding to TL in a molten globule state reestablishes tight packing around side chains that are oriented both inside and outside of the barrel. Unlike RBP and BLG; TL has no disulfide bond between G- and H-strands. It is likely that the central β-sheet in the molten globule state of lipocalins is stabilized by its interactions with the main α-helix, rather than the interstrand disulfide bond.