MARIA DOLORES PEREZ SANCHEZ, MARIA TERESA CORONADO PARRA, JESÚS BALTANAS COPADO, DAVID LOPEZ MARTINEZ, JUAN CARMELO GÓMEZ FERNÁNDEZ, MARIA SENENA CORBALÁN GARCÍA,

• [GI/IMIB/C070/2011] Biomembranas y Señalización Celular

The C2 domains are protein modules frequently involved in targeting proteins to cell membranes. They share a common fold of two four-stranded-?-sheets arranged in a compact ?-sandwich and surrounded by variable loops and helices, whose variations in the aminoacidic composition give them the capacity to bind phospholipids in a calcium-dependent manner.

By using a combination of biophysical and biochemical techniques like X-ray crystallography, isothermal titration calorimetry, dynamic light scattering and lipid binding assays,

we have shown for numerous C2 domains that they interact differently with Ca2+, phosphatidylserine and phosphoinositides, conferring different functional abilities to dock at the plasma membrane with different target messenger affinity mechanism. Moreover, we have shown that the C2A domain of synaptotagmin 1 is a non- PI(4,5)P2 responder because of a glutamic residue instead of one critical lysine. Different affinities to bind different phosphoinositides in membrane models are controlled by other amino acidic residues adjacent to the key interacting lysines.

Our discovers shed light on how these domains develop structural changes to modulate their sensitivity and specificity to various cellular signals, and provide structural and functional description about in what manner, C2 domains are controlled by a dual-target mechanism.