Subunit channeling

Structure of ATP synthase. The F complex situated above the membrane consists of three afi dimers and single y, S, subunits. The membrane segment Fq, also known as a stalk, consists of H" " channels. Protons are conducted via the C-subunit channels. The rotation of C-subunits relative to a subunit of the stalk drives the rotation of the )/-subunit. [Reproduced with permission from Y. Zhou, T. M. Duncan and R. L. Crass Subunit rotation in Escherichia coli FflFi-ATP synthase during oxidative phosphorylation. Proc. Natl. Acad. Sci. 94, 10583 (1997). [ 1997 by the National Academy of Sciences.]... 

An adequate proton supply to an F0 subunit channel in the mitchondrial ATP synthase is less certain. Using the same logic as before, proton supply from the cytosol at pH 7.5 would be only 20 H+ per channel per second. This discrepancy might be overcome by a much wider channel mouth, a slower rate of ATP synthesis per enzyme, or some additional mechanism by which protons are supplied to the mitochondrial ATP synthase. One possibility is that in mitochondria, where ATP synthesis (and therefore proton flux) is driven by a membrane potential, hydrolysis of water at the channel mouth could be a major source for protons. Kasianowicz et al. (46) found it necessary to invoke this possibility to account for the observed rates of protonophore-mediated proton conductance across lipid bilayers. 

Monomers in EcFtna are believed to reside mainly at site C on the inner surface and those in HuHF mainly in the three-fold inter subunit channels [67]. 

Figure 10.1. Structural components in the hydrogenase mechanism, shown for H2 - 2H+ + 2e in NiFe active sites. The reversible electron pathway is facilitated by three Fe-S clusters that act as stepping stones-to the surface of the small subunit, where there is a potential docking site for a c-type cytochrome. The proton channel is proposed to consist of a chain of proton-carrying amino acid residues leading to the surface of the large subunit. Channels for H2 ingress/egress have been identified.

Fig. 1. Model of a ligand gated ion channel (LGIC) where (a) is the structure of a generic LGIC subunit showing the two cysteine (Cys) residues common to all LGIC subunits, and (b) shows the arrangement of five such subunits as a pentamer having psuedo-cyclic symmetry delineating a gated, fluid-filled...

The PBRis distinct from the central BZ receptor although both can be present in the same tissues in differing ratios. PBRs are predominately localized on the outer mitochondrial membrane and are thus intracellular BZ recognition sites. The PBR is composed of three subunits an 18,000 mol wt subunit that binds isoquinoline carboxamide derivatives a 30,000 mol wt subunit that binds BZs and a 32,000 mol wt voltage-dependent anion channel subunit. The porphyrins may be endogenous ligands for the PBR. PBRs are involved in the control of cell proliferation and differentiation and steroidogenesis. 

The binding site is located at the tip of the subunit within the jelly roll structure (Figure 5.23). The sialic acid moiety of the hemagglutinin inhibitors binds in the center of a broad pocket on the surface of the barrel (Figure 5.24). In addition to this groove there is a hydrophobic channel that can accomodate large hydrophobic substituents at the C2 position of sialic acid (Figures 5.22 and 5.24). 

Figure 12.7 Ribbon diagram of one subunit of potin from Rhodobacter capsulatus viewed from witbin tbe plane of tbe membrane. Sixteen p strands form an antiparallel p barrel tbat traverses tbe membrane. Tbe loops at tbe top of tbe picture are extracellular whereas tbe short turns at tbe bottom face the periplasm. The long loop between p strands 5 and 6 (red) constricts the channel of the barrel. Two calcium atoms are shown as orange circles. (Adapted from S.W. Cowan, Curr. Opin. Struct. Biol. 3 501-507, 1993.)...

The complete porin molecule is a stable trimer of three identical subunits, three each with a functional channel (Figure 12.8). About one-third of the... 

The K+ channel is a tetrameric molecule with one ion pore in the interface between the four subunits... 

The polypeptide chain of the bacterial channel comprises 158 residues folded into two transmembrane helices, a pore helix and a cytoplasmic tail of 33 residues that was removed before crystallization. Four subunits... 

Figure 12.9 Schematic diagram of the stmc-ture of a potassium channel viewed perpendicular to the plane of the membrane. The molecule is tetrameric with a hole in the middle that forms the ion pore (purple). Each subunit forms two transmembrane helices, the inner and the outer helix. The pore heJix and loop regions build up the ion pore in combination with the inner helix. (Adapted from S.A. Doyle et al., Science 280 69-77, 1998.)...

Figure 12.10 Diagram showing two subunits of the channel, illustrating the way the selectivity filter is formed. Main-chain atoms line the walls of this narrow passage with carbonyl oxygen atoms pointing into the pore, forming binding sites for ions. (Adapted from D.A. Doyle et al., Sdence 280 69-77, 1998.)...

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. 

All K channels are tetrameric molecules. There are two closely related varieties of subunits for K channels, those containing two membrane-spanning helices and those containing six. However, residues that build up the ion channel. Including the pore helix and the inner helix, show a strong sequence similarity among all K+ channels. Consequently, the structural features and the mechanism for ion selectivity and conductance described for the bacterial K+ channel in all probability also apply for K+ channels in plant and animal cells. 

Like the photosynthetic reaction center and bacteriorhodopsin, the bacterial ion channel also has tilted transmembrane helices, two in each of the subunits of the homotetrameric molecule that has fourfold symmetry. These transmembrane helices line the central and inner parts of the channel but do not contribute to the remarkable 10,000-fold selectivity for K+ ions over Na+ ions. This crucial property of the channel is achieved through the narrow selectivity filter that is formed by loop regions from thefour subunits and lined by main-chain carbonyl oxygen atoms, to which dehydrated K ions bind. 

Figure 18.3 Protein crystals contain large channels and holes filled with solvent molecules, as shown in this diagram of the molecular packing in crystals of the enzyme glycolate oxidase. The subunits (colored disks) form octamers of molecular weight around 300 kDa, with a hole in the middle of each of about 15 A diameter. Between the molecules there are channels (white) of around 70 A diameter through the crystal. (Courtesy of Ylva Lindqvist, who determined the structure of this enzyme to 2.0 A resolution in the laboratory of Carl Branden, Uppsala.)...

Back A hand-drawn image of the potassium channel, in the same view as on the front cover, with each subunit of the tetrameric protein shown in a different color. 

FIGURE 10.33 The structure of the heptameric channel formed by o -hemolysin. Each of the seven subunits contributes a /3-sheet hairpin to the transmembrane channel. 

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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