Transmembrane a-helix

Figure 12.1 Four different ways in which protein molecules may be bound to a membrane. Membrane-bound regions are green and regions outside the membrane are red. Alpha-helices are drawn as cylinders and P strands as arrows. From left to right are (a) a protein whose polypeptide chain traverses the membrane once as an a helix, (b) a protein that forms several transmembrane a helices connected by hydrophilic loop regions,...

Gram-negative bacteria are surrounded by two membranes, an inner plasma membrane and an outer membrane. These are separated by a periplasmic space. Most plasma membrane proteins contain long, continuous sequences of about 20 hydrophobic residues that are typical of transmembrane a helices such as those found in bacteriorhodopsin. In contrast, most outer membrane proteins do not show such sequence patterns. 

Since the outside of the barrel faces hydrophobic lipids of the membrane and the inside forms the solvent-exposed channel, one would expect the P strands to contain alternating hydrophobic and hydrophilic side chains. This requirement is not strict, however, because internal residues can be hydrophobic if they are in contact with hydrophobic residues from loop regions. The prediction of transmembrane p strands from amino acid sequences is therefore more difficult and less reliable than the prediction of transmembrane a helices. 

The L and the M subunits are firmly anchored in the membrane, each by five hydrophobic transmembrane a helices (yellow and red, respectively, in Figure 12.14). The structures of the L and M subunits are quite similar as expected from their sequence similarity they differ only in some of the loop regions. These loops, which connect the membrane-spanning helices, form rather flat hydrophilic regions on either side of the membrane to provide interaction areas with the H subunit (green in Figure 12.14) on the cytoplasmic side and with the cytochrome (blue in Figure 12.14) on the periplasmic side. The H subunit, in addition, has one transmembrane a helix at the car-boxy terminus of its polypeptide chain. The carboxy end of this chain is therefore on the same side of the membrane as the cytochrome. In total, eleven transmembrane a helices attach the L, M, and H subunits to the membrane. 

Figure 12.14 The three-dimensional structure of a photosynthetic reaction center of a purple bacterium was the first high-resolution structure to be obtained from a membrane-bound protein. The molecule contains four subunits L, M, H, and a cytochrome. Subunits L and M bind the photosynthetic pigments, and the cytochrome binds four heme groups. The L (yellow) and the M (red) subunits each have five transmembrane a helices A-E. The H subunit (green) has one such transmembrane helix, AH, and the cytochrome (blue) has none. Approximate membrane boundaries are shown. The photosynthetic pigments and the heme groups appear in black. (Adapted from L. Stryer, Biochemistry, 3rd ed. New York ...

This symmetry is important in bringing the two chlorophyll molecules of the "special pair" into close contact, giving them their unique function in initiating electron transfer. They are bound in a hydrophobic pocket close to the symmetry axis between the D and E transmembrane a helices of both... 

Transmembrane a helices can be predicted from amino acid sequences... 

Membrane lipids have no specific interaction with protein transmembrane a helices... 

Bacteriorhodopsin contains seven transmembrane a helices Bacteriorhodopsin is a light-driven proton pump... 

The ion pore has a narrow ion selectivity filter The bacterial photosynthetic reaction center is built up from four different polypeptide chains and many pigments The L, M, and H subunits have transmembrane a helices... 

Hydrophobicity plots of AQPs indicated that these proteins consist of six transmembrane a-helices (Hl-H6 in Fig. la) connected by five connecting loops (A-E), and flanked by cytosolic N- and C-termini. The second half of the molecule is an evolutionary duplicate and inverse orientation of the first half of the molecule. Loops B and E of the channel bend into the membrane with an a-helical conformation (HB, HE in Fig. lb) and meet and each other at their so-called Asn-Pro-Ala (NPA) boxes. These NPA motifs are the hallmark of AQPs and form the actual selective pore of the channel, as at this location, the diameter is of that of a water molecule (3 A Fig. la and b). Based on the narrowing of the channel from both membrane sides to this small... 

Figure 23 Amino-acid sequence of bR by taking into account the secondary structure revealed by X-ray diffraction studies. All Ala and Val residues labelled by [13C]Ala and [l-,3C]Val are indicated by the circles and boxes, respectively. A-G denotes the seven transmembrane a-helical segments revealed by X-ray diffraction and G denotes the a-helical segments as revealed by NMR measurements.

A160G mutant (open circles) against temperature. (A) Alal03 (C-D loop), (B) Ala39 (helix B), 168 (helix F), (C) Ala228, 233 (C-terminal a-helix), D-F (transmembrane a-helices). From Ref. 192 with permission. 

Figure 36 Schematic representation of dynamic picture of bR in monomer. See the correlation times for the cytoplasmic and extracellular loops and transmembrane a-helices are significantly shortened as compared with those in 2D crystal as shown in Figure 24.

IkSnin, I. Pohorille, A. Chipot, C., Insights into the recognition and association of transmembrane a-helices. The free energy of a-helix dimerization in glycophorin A., J. Am. Chem. Soc. 2005,127, 8478-8484... 

Table I gives a compilation of the molecular composition of SFV grown in BHK-21 cells, based on the revised weight for the viral particle of 41-42 X 10 daltons (Jacrot et al, 1983). If one assumes that each phospholipid-cholesterol pair takes up a surface area of about 90-100 A (Israelachvili and Mitchell, 1975) and each glycolipid about 55 A (Pascher and Sundell, 1977), then about 80% of the surface area in the bilayer is occupied by the lipids, leaving about 20% for the spanning proteins. This is somewhat more than would be expected if 180 spike proteins span the bilayer, each having two transmembrane a helical segments.

N. Naarmann, B. Bilgiger, H. Meng, K. Kumar, C. Steinem, Fluorinated interfaces drive self-association of transmembrane a helices in lipid bilayers, Angew. Chem. Int. Ed. 45 (2006) 2588-2591. 

---