Channel-forming polypeptides, membrane

Polypeptide chains are transported across the membrane through an aqueous channel formed from membrane proteins. This protein-conducting channel is transiently formed so that a polypeptide chain can move across the pho-spholipid bilayer. The protein-conducting channel exists for both co- and post-translational processes and opens in two dimensions, i.e. perpendicular to the membrane to let hydrophilic polypeptide chains cross, and within the plane of the membrane to let hydrophobic anchors of membrane proteins into the phospholipid bilayer. 

Karle, I.L. Perozzo, M.A. Mishra, V.K. Balaram. P. Crystal stmcture of the channel-forming polypeptide anti-amoebin in a membrane-mimetic environment. Proc. Natl. 

In analogy to a series of polypeptide channel forming quasi ionophores, a model of pardaxin tetramer in water and in the membrane is presented ... 

FIGURE 11-8 Integral membrane proteins. For known proteins of the plasma membrane, the spatial relationships of protein domains to the lipid bilayer fall into six categories. Types I and II have only one transmembrane helix the amino-terminal domain is outside the cell in type I proteins and inside in type II. Type III proteins have multiple transmembrane helices in a single polypeptide. In type IV proteins, transmembrane domains of several different polypeptides assemble to form a channel through the membrane. Type V proteins are held to the bilayer primarily by covalently linked lipids (see Fig. 11-14), and type VI proteins have both transmembrane helices and lipid (GPI) anchors. 

In nature, polypeptides with amphiphilic structures are known to form transmembrane channels formed by an assembly of several helices, so as to present their polar faces inward and their apolar faces outward. In view of such behavior, the photochromic amphiphilic polypeptide was incorporated into a cationic bilayer membrane composed of dipalmitoyl phosphatidyl choline.11201 Fluorescence and microscopic measurements provided evidence that the polypeptide was able to form bundles of helical molecules analogous to their natural counterparts, which acted as transmembrane channels for K+ ions. Irradiation, and the consequent transacts isomerization of the azobenzene link, caused a bending of the molecular structure and a destabilization of the transmembrane bundles. Therefore, formation of ion permeable channels would be favored or inhibited depending on whether the azo moiety... 

ATP synthase activity can be restored by adding back the F] complex to the depleted membranes. The F[ complexes bind to membrane channels known as the F complex, which are also composed of multiple subunits. The polypeptides of the F0 component are very hydrophobic and form a proton transport channel through the membrane, which links the proton gradient to ATP synthesis. This channel appears to be lined with hydrophilic residues such as seryl, threonyl and carboxyl groups. The stalk that connects the F, to the F complex comprises one copy each of the polypeptide known as the oligomycin-sensitivity-conferring protein (OSCP) and another protein known as F6. 

Botulinum and tetanus neurotoxins, which are extensively soluble in water, are known to form efficient membrane channels at a low pH in artificial membranes (Hoch et al. 1985 Boquet and Duflot, 1982). Membrane channel formation by a water soluble protein is an intriguing phenomenon, because for water solubility, hydrophobic domains are needed on the surface of a protein whereas for membrane channel formation, adequate hydrophobic segments will be required for the interaction with non-polar membrane bilayer. A major question to be answered is how are the polypeptides integrated in the lipid bilayer. Are the hydrophobic segments of these neurotoxins hidden in aqueous medium which get exposed... 

The C-terminal transmembrane helix, the inner helix, faces the central pore while the N-terminal helix, the outer helix, faces the lipid membrane. The four inner helices of the molecule are tilted and kinked so that the subunits open like petals of a flower towards the outside of the cell (Figure 12.10). The open petals house the region of the polypeptide chain between the two transmembrane helices. This segment of about 30 residues contains an additional helix, the pore helix, and loop regions which form the outer part of the ion channel. One of these loop regions with its counterparts from the three other subunits forms the narrow selectivity filter that is responsible for ion selectivity. The central and inner parts of the ion channel are lined by residues from the four inner helices. 

ATP synthase actually consists of two principal complexes. The spheres observed in electron micrographs make up the Fj unit, which catalyzes ATP synthesis. These Fj spheres are attached to an integral membrane protein aggregate called the Fq unit. Fj consists of five polypeptide chains named a, j3, y, 8, and e, with a subunit stoichiometry ajjSaySe (Table 21.3). Fq consists of three hydrophobic subunits denoted by a, b, and c, with an apparent stoichiometry of ajbgCg.ig- Fq forms the transmembrane pore or channel through which protons move to drive ATP synthesis. The a, j3, y, 8, and e subunits of Fj contain 510, 482, 272, 146, and 50 amino acids, respectively, with a total molecular mass... 

Certain microbes synthesize small organic molecules, ionophores, that function as shuttles for the movement of ions across membranes. These ionophores contain hy-drophihc centers that bind specific ions and are surrounded by peripheral hydrophobic regions this arrangement allows the molecules to dissolve effectively in the membrane and diffuse transversely therein. Others, Hke the well-smdied polypeptide gramicidin, form channels. 

It has been known for some years that gramicidin forms transmembrane ion channels in lipid bilayers and biological membranes and that these channels are assembled from two molecules of the polypeptide 213). The channels are permeable specifically to small monovalent cations [such as H+, Na+, K+, Rb+, Cs+, Tl+, NH4+, CHjNHj, but not (CH3)2NH2+J and small neutral molecules (such as water, but not urea). They do not allow passage of anions or multivalent cations 21 n. 

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