Figure 10–18 Membrane protein attachment by a fatty acid chain or a prenyl group. the covalent attachment of either type of lipid can help localize a water-soluble protein to a membrane after its synthesis in the cytosol. (A) A fatty acid chain (myristic acid) is attached via an amide linkage to an n-terminal glycine.
(B) A fatty acid chain (palmitic acid) is attached via a thioester linkage to a cysteine. (c) A prenyl chain (either farnesyl or a longer geranylgeranyl chain) is attached via a thioether linkage to a cysteine residue that is initially located four residues from the protein’s c-terminus. After prenylation, the terminal three amino acids are cleaved off, and the new c-terminus is methylated before insertion of the anchor into the membrane (not shown). the structures of the lipid anchors are shown below: (D) a myristoyl anchor (derived from a 14-carbon saturated fatty acid chain), (e) a palmitoyl anchor (a 16-carbon saturated fatty acid chain), and (F) a farnesyl anchor (a 15-carbon unsaturated hydrocarbon chain).
Figure 10–19 a segment of a membrane-spanning polypeptide chain crossing the lipid bilayer as an α helix. Only the α-carbon backbone of the polypeptide chain is shown, with the hydrophobic amino acids in green and yellow. the polypeptide segment shown is part of the bacterial photosynthetic reaction center, the structure of which was determined by x-ray diffraction. (Based on data from J. Deisenhofer et al., Nature 318:618– 624, 1985, and h. Michel et al., EMBO J. 5:1149–1158, 1986.) membrane proteins at one moment and soluble proteins at the next. Such highly dynamic interactions greatly expand the repertoire of membrane functions.
In Most transmembrane proteins, the polypeptide chain crosses the lipid Bilayer in an α-helical conformation
A transmembrane protein always has a unique orientation in the membrane. This reflects both the asymmetric manner in which it is inserted into the lipid bilayer in the ER during its biosynthesis (discussed in Chapter 12) and the different functions of its cytosolic and noncytosolic domains. These domains are separated by the membrane-spanning segments of the polypeptide chain, which contact the hydrophobic environment of the lipid bilayer and are composed largely of amino acids with nonpolar side chains. Because the peptide bonds themselves are polar and because water is absent, all peptide bonds in the bilayer are driven to form hydrogen bonds with one another. The hydrogen-bonding between peptide bonds is maximized if the polypeptide chain forms a regular α helix as it crosses the bilayer, and this is how most membrane-spanning segments of polypeptide chains traverse the bilayer (Figure 10–19).
In single-pass transmembrane proteins, the polypeptide chain crosses only once (see Figure 10–17, example 1), whereas in multipass transmembrane proteins, the polypeptide chain crosses multiple times (see Figure 10–17, example 2). An alternative way for the peptide bonds in the lipid bilayer to satisfy their hydrogen-bonding requirements is for multiple transmembrane strands of a polypeptide chain to be arranged as a βsheet that is rolled up into a cylinder (a so-called β barrel; see Figure 10–17, example 3). This protein architecture is seen in the
Figure 10–20 Using hydropathy plots to porin proteins that we discuss later.