Extramembrane region

Glutamic acid is an electrically charged amino acid. Charged amino acid residues in membrane proteins possess an environment that is very well defined, that is, they are very rarely present in the membrane and are predominantly located in extramembrane regions. Glutamic acid may be found in the membrane only if its environment possesses a high propensity for finding it in the membrane. 

Each of 7 of 10 nuclear-encoded subunits has a single transmembrane helix. The largest nuclear-encoded subunit, subunit IV, resembles a dumbbell with two extramembrane moieties. Subunit Vic also has two extramembrane moieties on both sides, one of which is in an extended conformation protruding to the matrix space (Fig. 7D). Subunits Vila, Vllb, VIIc, and VIII, each with an extramembrane moiety on one end, look like screws (Fig. 7). Subunit Via also has only one extramembrane moiety on the intermembrane side. However, 10 residues of the N-terminal are in an extended conformation and make contact with two a-hehces of subunit I of the other monomer in the transmembrane region. Thus, this moiety provides a U-shaped turn near the N-terminus. The bridging contact contributes to the stability of the dimer state. 

A specific phospholipid requirement has been determined for optimum in vitro reconstitution of function for more than 50 membrane proteins. If one considers specific lipid requirements for membrane association and activation of amphitropic proteins, the number is in hundreds. Integral membrane proteins fold and exist in a very complex environment and have three modes of interaction with their environment. The extramembrane domains are exposed to the water milieu, where they interact with water, solutes, ions, and water-soluble proteins. Part of the protein is exposed to the hydrophobic-aqueous interface region (Fig. 9). The remainder of the protein is buried within the approximately 30-A thick hydrophobic interior of the membrane. Amphitropic proteins may spend part of their time completely in the cytosol and are recruited to the membrane surface, or even partially inserted into the membrane, in response to various signals. 

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