Internally bridging water molecule in transmembrane α-helical kink

There are hundreds of membrane protein atomic coordinates in the Protein Data Bank (PDB), and high-resolution structures of better than 2.5 Å enable the visualization of a sizable number of amphiphiles (lipid and/or detergent) and bound water molecules as essential parts of the structure. Upon scrutinizing these high-resolution structures, water molecules were found to ‘wedge’ and stabilize large kink angle (30–40°) in a simple cylindrical model at the transmembrane helical kinks so as to form an inter-helical cavity to accommodate a ligand binding or active site as a crucial structural feature in α-helical integral membrane proteins. Furthermore, some of these water molecules are proposed to play a pivotal role of their conformational change to exert their functional regulation.