Effect of calcium and cholesterol on membrane binding and localization of the S100A16 protein

Maintaining the structural and functional integrity of cellular membranes is essential for proper cells function. A recent proteomic study suggests that the S100A16 protein may contribute to the maintenance of membrane integrity in the rod outer segment (ROS) of photoreceptor cells in the eye. The protein S100A16, one of the most recently identified members of the S100 protein family, remains among the few S100 proteins for which no protein-membrane interactions have yet been characterized. Importantly, membrane integrity is known to be a calcium-sensitive process. The polar headgroup composition of the human ROS consists of approximately 32.5% of phosphatidylcholine, 37.6% of phosphatidylethanolamine, and 12.1% of phosphatidylserine. In addition, polyunsaturated chains account for 30-60% of the total lipid fraction in humans. Cholesterol concentration within the ROS disc membranes varies from 5 to 30% between the base and the summit of the outer segment. To investigate potential membrane interactions of S100A16 and to better understand its localization and involvement in membrane-associated processes, a Langmuir monolayer model was combined with surface tensiometry. The results clearly indicate that S100A16 preferentially interacts with saturated phospholipids with short acyl chains and zwitterionic polar head group, as well as with membrane domains enriched with cholesterol. These preferential lipid interactions suggest that the S100A16 may interact primarily with the plasma membrane and nascent disk membranes in the outer segments of photoreceptors, contributing to membrane integrity in these highly dynamic regions.