Proteins extramembrane domains

In this figure, and in figures throughout the book, we represent transmembrane protein segments in their most likely conformations as a helices of six to seven turns. Sometimes these helices are shown simply as cylinders. As relatively few membrane protein structures have been deduced by x-ray crystallography, our representation of the extramembrane domains is arbitrary and not necessarily to scale. 

Is the manner in which transmembrane (TM) helices pack together dictated by the sequences contained within the membrane or by the extramembranous sequences, or loops There is now considerable evidence that most loops are not essential in specifying the fold of membrane proteins. First, in many cases, the TM helices can encode considerable information for specifying the fold. Many single TM helices, such as the TM helix from glycophorin A, self-associate in the absence of their extramembranous domains (Lemmon et al., 1992a,b). Second, there are many examples in which the loops between TM helices in... 

A completely different principle has been followed by the heptameric a-hemolysines (Song et al., 1996 Olson et al., 1999). These proteins associate with their extramembrane domains. Subsequently, each subunit donates a /3-hairpin to form a common 14-stranded /3-barrel through the membrane. In a similar manner TolC is assembled from three a-helical subunits (Koronakis et al., 2000). The subunits form a long, wide channel that spans the periplasm in their a-helical part and that is prolonged through the outer membrane by the /3-barrel. The channel is used for the export of xenobiotics. 

The spaciousness of the ionic reservoir of tBLMs may not be sufficient to accommodate bulky extramembrane domains of membrane proteins. The problem is... 

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. 

Based on statistical analysis and experimental determination, the cytoplasmic extramembrane domains connecting transmembrane domains predominantly carry a positive charge in contrast to the remaining extramembrane domains that are either neutral or negative (positive inside rule) [24]. Although amino acid sequence determines membrane protein topology, the sequence is encoded for a specific membrane lipid environment as has been demonstrated for the secondary transport proteins of E. coli. Reducing the net positive... 

Interpretation of the membrane proteins in an envelope virus can be assisted by the identification of transmembrane a helices. Membrane proteins represent a special class of proteins because of the predominant presence of transmembrane helices connected by extramembrane loops and domains. For example, even at 10.5-A resolution, a pair of transmembrane helices could be identified in the Semliki Forest virus El and E2 proteins (Eig. 10 see Color Insert). 

Much less is known about the role of phospholipids in insertion and organization of integral membrane proteins than about the protein machinery required for protein insertion. Most membrane proteins are organized with several a-helical transmembrane domains spanning the membrane bilayer. These helices are connected by extramembrane loops alternately exposed on either side of the membrane. How do lipids act in specific ways to guide and determine final membrane protein structure and organization ... 

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