Proteins integral membrane

Mothes, W., Heinrich S., Graf, R., Nilsson, I., von Heijne, G., Brunner,J., and Rapoport, T. (1997). Molecular mechanism of membrane protein integration into the endoplasmic reticulum. CeU 89, 523-533. 

Liao S, Lin J, Do H, Johnson AE (1997) Both lumenal and cytosolic gating of die aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration. Cell 90 31-41 Liebman SW, Sherman F (1976) Inhibition of growth by amber suppressors in yeast. Genetics 82 233-249 Liebman SW, Chernoff YO, Liu R (1995) The accuracy center of a eukaryotic ribosome. Biochem Cell Biol... 

Single transmembrane helix Ca2+ receptor N terminus in vesicle SNARE proteins, C termini in vesicle Integral membrane protein Integral membrane protein, Cl- transporter Integral membrane protein Integral membrane protein 13 subunits H+ generator... 

However, it is already clear that the mechanisms responsible for membrane protein integration into the ER membrane and the inner bacterial membrane do place certain constraints on the allowable structures... 

Hermansson, M., Monne, M., and von Heijne, G. (2001). Formation of helical hairpins during membrane protein integration into the ER membrane. Role of the N- and C-terminal flanking regions./ Mol. Biol. 313,1171-1179. 

Figure 12.17. Integral and Peripheral Membrane Proteins. Integral membrane proteins (a, b, and c) interact extensively with the hydrocarbon region of the bilayer. Nearly all known integral membrane proteins traverse the lipid bilayer. Peripheral membrane proteins d and e) bind to the surfaces of integral proteins. Some peripheral membrane proteins interact with the polar head groups of the lipids (not shown).

Mothes, W., et al. 1997. Molecular mechanism of membrane protein integration into the endoplasmic reticulum. Ceil 89 523-533. 

Figure 2 Various types of membrane proteins. Integral membrane proteins may cross the lipid bilayer several times (a) or once (b). Peripheral membrane proteins are associated with the hydrophilic outer part of the lipid bilayer (c).

At a low concentration of detergent, mainly hydrophilic proteins were eluted during the salt gradient [29]. A second step with a high concentration of detergent in the elution buffer resulted in elution of the membrane proteins. Integral membrane proteins of Sendai virus [29], herpes simplex virus [30,30a], and Plasmodium falciparum [31 ] were purified by this approach. 

Cowan, S.W., Rosenbusch, J.R Folding pattern diversity of integral membrane proteins. Science 264 914-916, 1994. 

Garavito, R.M., Rosenbusch, J.R Three-dimensional crystals of an integral membrane protein an initial x-ray analysis. /. Cell. Biol. 86 327-329, 1980. 

Just how fast can proteins move in a biological membrane Many membrane proteins can move laterally across a membrane at a rate of a few microns per minute. On the other hand, some integral membrane proteins are much more restricted in their lateral movement, with diffusion rates of about 10 nm/sec or even slower. These latter proteins are often found to be anchored to the cytoskeleton (Chapter 17), a complex latticelike structure that maintains the cell s shape and assists in the controlled movement of various substances through the ceil. 

There are other ways in which the lateral organization (and asymmetry) of lipids in biological membranes can be altered. Eor example, cholesterol can intercalate between the phospholipid fatty acid chains, its polar hydroxyl group associated with the polar head groups. In this manner, patches of cholesterol and phospholipids can form in an otherwise homogeneous sea of pure phospholipid. This lateral asymmetry can in turn affect the function of membrane proteins and enzymes. The lateral distribution of lipids in a membrane can also be affected by proteins in the membrane. Certain integral membrane proteins prefer associations with specific lipids. Proteins may select unsaturated lipid chains over saturated chains or may prefer a specific head group over others. 

Membrane proteins in many cases are randomly distributed through the plane of the membrane. This was one of the corollaries of the fluid mosaic model of Singer and Nicholson and has been experimentally verified using electron microscopy. Electron micrographs show that integral membrane proteins are often randomly distributed in the membrane, with no apparent long-range order. 

ITowever, membrane proteins can also be distributed in nonrandom ways across the surface of a membrane. This can occur for several reasons. Some proteins must interact intimately with certain other proteins, forming multisubunit complexes that perform specific functions in the membrane. A few integral membrane proteins are known to self-associate in the membrane, forming large multimeric clusters. Bacteriorhodopsin, a light-driven proton pump protein, forms such clusters, known as purple patches, in the membranes of Halobacterium halobium (Eigure 9.9). The bacteriorhodopsin protein in these purple patches forms highly ordered, two-dimensional crystals. 

Discuss the effects on the lipid phase transition of pure dimyris-toyl phosphatidylcholine vesicles of added (a) divalent cations, (b) cholesterol, (c) distearoyl phosphatidylserine, (d) dioleoyl phosphatidylcholine, and (e) integral membrane proteins. 

Garavito, R. M., et al., 1983. X-ray diffraction analysis of matrix porin, an integral membrane protein from Escherichia coli outer membrane. Journal of Nlolecular Biology 164 313—327. 

FIGURE 15.21 Hormone (H) binding to its receptor (R) creates a hormone receptor complex (H R) that catalyzes GDP-GTP exchange on the o -subunit of the heterotrimer G protein (G ), replacing GDP with GTP. The G -subunit with GTP bound dissociates from the /37-subunits and binds to adenylyl cyclase (AC). AC becomes active upon association with G GTP and catalyzes the formation of cAMP from ATP. With time, the intrinsic GTPase activity of the G -subunit hydrolyzes the bound GTP, forming GDP this leads to dissociation of G GDP from AC, reassociation of G with the /Sy subunits, and cessation of AC activity. AC and the hormone receptor H are integral plasma membrane proteins G and G are membrane-anchored proteins. 

Complex II is perhaps better known by its other name—succinate dehydrogenase, the only TCA cycle enzyme that is an integral membrane protein in the inner mitochondrial membrane. This enzyme has a mass of approximately 100 to 140 kD and is composed of four subunits two Fe-S proteins of masses 70 kD and 27 kD, and two other peptides of masses 15 kD and 13 kD. Also known as flavoprotein 2 (FP2), it contains an FAD covalently bound to a histidine residue (see Figure 20.15), and three Fe-S centers a 4Fe-4S cluster, a 3Fe-4S cluster, and a 2Fe-2S cluster. When succinate is converted to fumarate in the TCA cycle, concomitant reduction of bound FAD to FADHg occurs in succinate dehydrogenase. This FADHg transfers its electrons immediately to Fe-S centers, which pass them on to UQ. Electron flow from succinate to UQ,... 

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... 

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