Ha

hairpins

Unstable void space

Inner leaflets of both membranes come into contact.

Zipping causes curvature and lateral tension on bilayers, favoring hemifusion between outer leaflets and causing formation of an energetically unfavorable void space.

Unstable void space

Inner leaflets of both membranes come into contact.

HA fusion peptide creates local disruption of bilayer, and hemifusion occurs; outer monolayer of virus fuses with inner monolayer of endosome.

HA fusion peptide creates local disruption of bilayer, and hemifusion occurs; outer monolayer of virus fuses with inner monolayer of endosome.

Pore widens; vesicle contents are released outside cell.

FIGURE 11-24 Fusion induced by the hemagglutinin (HA) protein during viral infection. HA protein is exposed on the membrane surface of the influenza virus. When the virus moves from the neutral pH of the interstitial fluid to the low-pH compartment (endosome) in the host cell, HA undergoes dramatic shape changes that mediate fusion of the viral and endosomal membranes, releasing the viral contents into the cytoplasm.

FIGURE 11-25 Fusion during neurotransmitter release at a synapse.

The membrane of the secretory vesicle contains the v-SNARE synap-tobrevin (red). The target (plasma) membrane contains the t-SNAREs syntaxin (blue) and SNAP25 (violet). When a local increase in [Ca2+] signals release of neurotransmitter, the v-SNARE, SNAP25, and t-SNARE interact, forming a coiled bundle of four a helices, pulling the two membranes together and disrupting the bilayer locally, which leads to membrane fusion and neurotransmitter release.

domains. Complete fusion results in release of the viral contents into the host cell cytoplasm.

Neurotransmitters are released at synapses when intracellular vesicles loaded with neurotransmitter fuse with the plasma membrane. This process involves a family of proteins called SNARES (Fig. 11-25). SNARE s in the cytoplasmic face of the intracellular vesicles are called v-SNAREs; those in the target membranes with which the vesicles fuse (the plasma membrane during exocytosis) are t-SNAREs. Two other proteins, SNAP25 and NSF, are also involved. During fusion, v- and t-SNAREs bind to each other and undergo a structural change that produces a bundle of long thin rods made up of helices from both v- and t-SNARES and two helices from SNAP25 (Fig. 11-25). The two SNAREs initially interact at their ends, then zip up into the bundle of helices. This structural change pulls the two membranes into contact and initiates the fusion of their lipid bilayers.

The complex of SNAREs and SNAP25 is the target of the powerful Clostridium botulinum toxin, a protease that cleaves specific bonds in these proteins, preventing neurotransmission and causing the death of the organism. Because of its very high specificity for these proteins, purified botulinum toxin has served as a powerful tool for dissecting the mechanism of neurotrans-mitter release in vivo and in vitro.

SUMMARY 11.2 Membrane Dynamics

■ Lipids in a biological membrane can exist in liquid-ordered or liquid-disordered states; in the latter state, thermal motion of acyl chains makes the interior of the bilayer fluid. Fluidity is affected by temperature, fatty acid composition, and sterol content.

■ Flip-flop diffusion of lipids between the inner and outer leaflets of a membrane is very slow except when specifically catalyzed by flippases.

■ Lipids and proteins can diffuse laterally within the plane of the membrane, but this mobility is limited by interactions of membrane proteins with internal cytoskeletal structures and interactions of lipids with lipid rafts. One class of lipid rafts consists of sphingolipids and cholesterol with a subset of membrane proteins that are GPI-linked or attached to several long-chain fatty acyl moieties.

■ Caveolin is an integral membrane protein that associates with the inner leaflet of the plasma membrane, forcing it to curve inward to form caveolae, probably involved in membrane transport and signaling.

■ Integrins are transmembrane proteins of the plasma membrane that act both to attach cells to each other and to carry messages between the extracellular matrix and the cytoplasm.

■ Specific proteins mediate the fusion of two membranes, which accompanies processes such as viral invasion and endocytosis and exocytosis.

11.3 Solute Transport across Membranes

Every living cell must acquire from its surroundings the raw materials for biosynthesis and for energy production, and must release to its environment the byproducts of metabolism. A few nonpolar compounds can dissolve in the lipid bilayer and cross the membrane unassisted, but for polar or charged compounds or ions, a membrane protein is essential for transmembrane movement. In some cases a membrane protein simply facilitates the diffusion of a solute down its concentration gradient, but transport often occurs against a gradient of concentration, electrical charge, or both, in which case solutes must be "pumped" in a process that requires energy (Fig. 11-26). The energy may come directly from ATP hydrolysis or may be supplied in the form of movement of another solute down its electrochemical gradient with enough energy to carry another solute up its gradient. Ions may also move across membranes via ion channels formed by proteins, or they may be carried across by ionophores, small molecules that mask the charge of the ions and allow them to diffuse through the lipid bilayer. With very few exceptions, the traffic of small molecules across the plasma membrane is mediated by proteins such as transmembrane channels, carriers, or pumps. Within the eukaryotic cell, different compartments have different concentrations of metabolic intermediates and products and of ions, and these, too, must move across intracellular membranes in tightly regulated, protein-mediated processes.

Passive Transport Is Facilitated by Membrane Proteins

When two aqueous compartments containing unequal concentrations of a soluble compound or ion are separated by a permeable divider (membrane), the solute moves by simple diffusion from the region of higher concentration, through the membrane, to the region of lower concentration, until the two compartments have equal solute concentrations (Fig. 11-27a). When ions of opposite charge are separated by a permeable membrane, there is a transmembrane electrical gradient, a membrane potential, Vm (expressed in volts or millivolts). This membrane potential produces a force opposing ion movements that increase Vm and driving ion movements that reduce Vm (Fig. 11-27b). Thus the direction in which a charged solute tends to move spontaneously across a membrane depends on both the

Simple diffusion (nonpolar compounds only, down concentration gradient)

Sout

Facilitated diffusion (down electrochemical gradient)

Ionophore-mediated ion transport (down electrochemical gradient)

Ion o

Ion channel (down electrochemical gradient; may be gated by a ligand or ion)

FIGURE 11-26 Summary of transport types.

Sout

Facilitated diffusion (down electrochemical gradient)

11 Habits To Make or Break For Soft Flawless Skin

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Habits to Break and Habits to Maintain for Dazzling Skin. As you all know, our skin is the obvious appearance of who or what we are, or perhaps would like to be. However, it is more than just a simple mask.

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