HIV, CD4, and Membrane Proteins

Membrane Structure and Function Overview

• Membrane structure, properties, and regulation of inbound/outbound traffic across the plasma membrane are key topics.

Fluid Mosaic Model

• Cellular membranes are fluid mosaics composed of lipids and proteins.
• Membranes consist mainly of lipids and proteins.
• Phospholipids, the most abundant lipid in the plasma membrane, are amphipathic molecules with hydrophobic and hydrophilic regions.
• Most membrane proteins and lipids are amphipathic.
• Membrane proteins reside in the phospholipid bilayer with hydrophilic regions protruding.
• Hydrophilic regions of proteins contact water in the cytosol and extracellular fluid, while hydrophobic parts are shielded in a nonaqueous environment.
• The plasma membrane is described by the term "fluid mosaic model".
• The fluid mosaic model describes the membrane as a mosaic of protein molecules bobbing in a fluid bilayer of phospholipids and other components (cholesterol). These components move freely within the membrane plane.

Membrane Fluidity

• Membranes are not static sheets of molecules rigidly locked in place
• Membranes are held together mainly by hydrophobic interactions, which are weaker than covalent bonds.
• Lipids shift about sideways; sideways movement of phospholipids within the membrane is rapid and adjacent phospholipids switch positions about 107 times per second.
• Lipids may flip-flop across the membrane, switching from one phospholipid layer to the other, but rarely.
• Membrane proteins can shift sideways like lipids but, being larger than lipids, move more slowly.
• Some proteins move in a highly directed manner, driven along cytoskeletal fibers by motor proteins.
• Many membrane proteins are held immobile by their attachment to the cytoskeleton or to the extracellular matrix.
• Membranes rich in unsaturated fatty acids are more fluid than those rich in saturated fatty acids.
• As temperatures cool, membranes switch from a fluid state to a solid state.
• The temperature at which a membrane solidifies depends on the types of lipids it is made from.
• As the temperature decreases, the membrane remains fluid at a lower temperature if composed of phospholipids with unsaturated hydrocarbon tails.
• Unsaturated hydrocarbon tails (kinked) prevent packing and enhance membrane fluidity.
• Saturated hydrocarbon tails pack together to increase membrane viscosity.
• Cholesterol acts as a "fluidity buffer" at different temperatures in the membrane.
• At warm temperatures (37°C), cholesterol restrains the movement of phospholipids
• At cool temperatures, it maintains this fluidity by preventing tight packing of phospholipids.
• Cholesterol reduces membrane fluidity at moderate temperatures by reducing phospholipid movement.
• At low temperatures, cholesterol hinders solidification by disrupting the regular packing of phospholipids.
• Membranes must be fluid to function; fluidity affects permeability and the movement of membrane proteins.

Membrane Lipid Composition

• Variations in lipid composition of cell membranes of many species appear to be adaptations to certain environmental conditions.
• Fish living in extreme cold have membranes with a high proportion of unsaturated hydrocarbon tails to remain fluid.
• Some bacteria and archaea organisms thrive at temperatures greater than 90°C in thermal hot springs and use unusual lipids to prevent excessive fluidity.
• Ability to change lipid compositions in response to temperature changes occurs in organisms that live where temperatures vary.
• Plants that tolerate extreme cold, such as winter wheat, increase the percentage of unsaturated phospholipids in autumn to keep membranes from solidifying during winter.
• Natural selection favors organisms with a membrane lipid mix ensures appropriate membrane fluidity for their environment.

Membrane Proteins

• Proteins determine most of the membranes function.
• Different cell types have different membrane protein sets, and each cell membrane has a unique protein collection.
• A single cell may have unique membrane proteins that carry out various functions. One protein may carry out multiple tasks on its own.
• More than 50 protein types in the plasma membrane of red blood cells.
• Integral proteins are permanently attached to the plasma membrane and are referred to as intrinsic proteins.
• Integral proteins are embedded in the whole membrane and interact strongly with the hydrophobic core of the lipid bilayer.
• Peripheral proteins are temporarily attached to the plasma membrane and referred to as extrinsic proteins.
• Peripheral proteins are often located on inner or outer surface of the phospholipid bilayer and interact less with the hydrophobic core of the lipid bilayer.
• Peripheral proteins are often held by the cytoskeleton.
• The structure of a transmembrane protein consists of a N-terminus outside the cell and a C-terminus inside.
• Hydrophobic regions consist of one or more stretches of nonpolar amino acids.
• Amino acids are typically 20-30 in length and usually coiled into a helices.
• Hydrophilic sections of molecule are exposed to the aqueous solutions on either side of the membrane.

Membrane Protein Function

• Six types of functions for membrane proteins
• Proteins that span the membrane may form hydrophilic channels for solutes (transport).
• Transport proteins can shuttle substances across the membrane by changing shape, hydrolyzing ATP to actively pump substances.
• Enzymes built into the membrane may have active sites that bind reactants in adjacent solutions (enzymatic activity)
• Several enzymes form a team for sequential steps in metabolic pathway.
• Membrane proteins (receptors) with specific binding sites fit the shape of chemical messengers (signal transduction).
• This messenger triggers protein shape change, relaying message to the inside of the cell, usually by binding to a cytoplasmic protein.
• Glycoproteins serve as identification tags specifically recognized by other cell membrane proteins (cell-cell recognition).
• This cell-cell binding is typically short-lived.
• Membrane proteins of adjacent cells may hook together in various junctions (intercellular joining) Some bind to microfilaments of the cytoskeleton or the extracellular matrix (ECM).
• This helps maintain cell shape, stabilizes membrane protein location and coordinates extracellular and intracellular changes.

Proteins and Medical Applications

• Proteins on the cell's surface are important in the medical field.
• CD4, a surface protein on immune cells, allows the human immunodeficiency virus (HIV) to infect these cells, leading to acquired immune deficiency syndrome (AIDS).
• Some HIV-exposed individuals to not develop AIDS and show no HIV-infected cells.
• This led to the HIV treatment that targets CCR5.

Membrane Carbohydrates

• Cell-cell recognition is when cells use another cell to distinguish one neighboring type from another.
• Cell-cell recognition is important in sorting cells into tissues/organs during animal embryo development.
• Serves as basis for immune system rejection of foreign cells, an important defense line in vertebrate animals.
• Cells know other cells by often binding often to molecules containing carbohydrates on the extracellular plasma membrane surface.
• Membrane carbohydrates are short, branched chains of fewer than 15 sugar units
• Some chains are covalently bonded to lipids, forming glycolipids
• some are covalently bonded to proteins, which form glycoproteins.
• Carbohydrates vary from species to species, from individual to individual, and even from one cell type to another.
• Diverse carbohydrates are markers that distinguish one cell from another.
• Human blood type differences (A, B, AB, O) reflect the carbohydrate parts of glycoproteins on red blood cells.

Membrane Synthesis

• Membranes posses distinct inside and outside faces.
• Lipid layers may differ in lipid composition.
• Each protein has directional orientation in the membrane.
• Asymmetrical distribution of proteins, lipids, and carbohydrates in the plasma membrane happens as membrane are built by the ER and Golgi apparatus.
• Carbohydrates are attached to plasma membrane proteins in the ER and are located to be located on to the inside of the transport vesicle membrane.

Selective Permeability

Selective permeability occurs to regulate inbound an outbound traffic across the plasma membrane

• A cell exchanges materials with its environment.
• Plasma membrane regulates movement of substances into/out of the cell and is called selectively permeable. A membrane allows some substances to cross more easily than others but blocks other materials from moving.
• Ability to regulate transport across boundaries is essential to the cell's existence.
• A steady traffic of molecules and ions moves across plasma membrane in both directions.
• Sugars, amino acids and other nutrients enter; metabolic waste products leave.
• The cell intakes O2 for cellular respiration while expelling CO2.
• Regulates inorganic ion concentrations (Na+, K+, Ca2+, and Cl-) by movement across the membrane.

Membrane Permeability

The permeability of the the lipid bilayer influences membrane transport

• Hydrophobic (nonpolar) molecules (hydrocarbons) dissolve in the lipid bilayer and pass directly through without assistance of membrane proteins.
• Polar & hydrophilic molecules, like sugars and ions, do not cross easily.
• Hydrophobic interior of the membrane prevents direct passage of ions and polar molecules as they are hydrophilic.

Molecules that can pass through the membrane

• The following molecules can pass through the membrane
• Lipid soluble molecules
• Oxygen (O2) and carbon dioxide (CO2)
• Small uncharged polar molecules (H2O)
• Fat soluble molecules
• Small non polar molecules
• The following molecules can not pass through the membrane
• Sugars
• Polar molecules
• Ions (charged particles)

Transport Proteins

• Transport proteins assist passage of hydrophilic substances across.
• Channel proteins facilitate by having a hydrophilic channel that molecules/ions use as a tunnel.
• Some function as aquaporins to allow the transport water across the membrane.
• Carrier proteins bind to molecules and change shape to shuttle them across

Passive Transport

• Passive transport is diffusion of a substance across a biological membrane with no energy investment.
• Water diffuses rapidly across cell membranes with aquaporins, compared to diffusion the absence of such proteins.
• The uptake of oxygen occurs when a cell performs cellular action Dissolved oxygen diffuses into the cell across the plasma membrane .
• The cellular respiration consumes 02 as it goes in. The diffussion into cell will continue because concentration gradient favors movement in the direction.

Facilitated Diffusion

• Many polar molecules/ions blocked by the lipid bilayer passively diffuse with the help of transport proteins that span membrane and use facilitated diffusion.
• In facilitated diffusion, transport proteins speed molecule movement across the plasma membrane. Two types of transport proteins used: channel proteins and carrier proteins.
• Channel proteins simply provide corridors that allow specific molecules or ions to cross the membrane.
• Hydrophilic passageways are proteins that allow quick diffusion of water or small ions across the membrane.
• Aquaporins (water channels) transport water.
• Ion channels transport ions; many function as gated channels that open/close due to a stimulus.
• Ion channels can be voltage-gated which open or close in response to an electrical stimulus such as potassium ion channels in neurons.
• Ligand-gated ion channels also open or close when a specific substance (not the one to be transported) binds to the channel
• Carrier proteins subtly change shape to translocate the solute-binding site across the membrane.
• The shape change is triggered by binding and release of the transported molecule

Simple vs Facilitated Diffusion

• This lists the differences between simple and facilitated diffusion -Simple diffusion is an unassisted type of diffusion in which a particle moves from a higher to a lower concentration -Facilitated diffusion is the transport of substances across biological membrane through concentration gradient by means of carrier protein. -One is a diffusion the phospholipid bilayer, where the other has transmembrane protien -One uses the transport of small, non-polar substances in contrast to large or polar particles -One has direct movement of molecules, where as, the other transport throught specific facilitator molecules.

Osmosis

-Osmosis is water diffusion across a selectively permeable membrane whether artificial or cellular.

• Water diffuses from high free water concentration (low solute concentration) to low water concentration (high solute concentration) until solute concentrations are equal.
• Water shifts from areas of low solute concentration to areas of high concentration.

Water Balance

The following section involves Water balance between living cells.

• Tonicity is the ability of a surrounding solution to cause a cell to gain or lose water.
• Tonicity of solution depends in part on its solutes that can't across the membrane (nonpenetrating solutes).
• Higher nonpenetrating solutes in surrounding solution, water leaves the cell, and reverse.
• Isotonic solution: Solute concentration is the same as inside the cell.
• Hypotonic solution: Solute concentration is greater than inside the cell.
• Hypertonic solution: solute concentration is less than that inside cell. The following properties are for solutions having equal osmotic pressures
• Have equal equal solute concentrations
• Environments show no effect on cells
• Are not helpful in food preservation

Solutions

• Hypotonic solutions having lower osmotic pressures.
• Isotonic Solutions having comparative higher osmotic pressure.
• Having a low concentration in hypotonic solutions where there is a high conctration in hypertonic
• Hypotonic environments cause cells to swell while hypertonic causes cells to shrink
• Are not helpful in food preservation, when hypertonic is helpful iin food preservation
• Cells may be in three different solutions where they lyses, shrinkeled, or become normal
• Having a low concentration in hypotonic solutions, while hypertonic enviroments cause cells to shrnik
• Cells can be exposed in different enviroments. Here are the properties for living cells exposed: -A rigid can't tolerate excess uptake and loss of rigid wall -Environments create osmotic problem with living cells -Are need an adapations to perform their functions

Osmoregulation

• It is the osmoregulation of solute and water, it is vital for cells to survive
• Some organisms such as protozoa have less that permeable due to constant uptake cell.
• It has a vacuoles contract and excess water and prevent bursting the cell

Cell walls & osmosis

• Plant Cell's with cell wall osmosis is a result of water enters a hypotonic solution
• the relatively in elastic which expands as water increase until a certain point. That pressure exerts pressure on the wall
• It is also described to be turgid, a healthy stae of plant cellls
• If plant cells with surrounding solution is too high, there is no room for the cell to move and it becomes flaccid with plants will be in its limp shape
• No advantage of cell walls in hypertonic eniroment
• Cells shrivlel and the cell wall is damaged. The Cell Shrinks the cell, it is called plasmolysis

Active Transport

• Active transport moves substances move against in higher concentration gradient. Which it uses the help of ATP.
• The transoprts proteins, that more solutes against the higher concentrations are called carrier proteins.
• This helps cell maintain intenral concertration
• Animal cells have a unique concentaration gradients like k+.

Membrane Potential

• An electrical potential which the animal transports.
• The side membrame is more negatively charge cause on distibution
• Number a small number of high pressure are responsible for membrane potential

Ions and the Membrane Potential

• It ranges with in range amount
• All cells within body haaev charateritic resting membrane and depends on cell type
• Only the neurons and muscle cells

Electrochemical gradient

• Drives the effusuons of across membranes
• The electrochemical gradient is more directly with concentration
• The concentration depends on the cell. Example; Gated Channels or diffusion.
• The pump generates a transport protien that genetate a cell as volgate

Electrogenic Pump

• Major electro pump of animal cells
• Pump does transfer sodium and potassium , the cell transports through extracellular

Proton Pump

• They pumps transport protiens through cell membrane
• Energy of dual is from the up take neutrient. Powered by ATP hydrolysis
• In plant cell its used transport amino acid

Couplet of Transport protiens

• It runs that transport with cotransporter
• It goes to a gradient of sugar
• Sodium is waste and abdorbed and is given a soluton drink high concentrations in cell
• It is used to help mortalatiy.

Traffic

• The bulk transport moves higher larger of molecuels. And they cant get access to the plasma membrane
• To the cell membrane the exositotis a very large in the cell to make a fussion cell as membrane -Cells in the insulin secrete. Cell need to make in order to release neutro transmitter

endocytosis

• Cells are taken molecules to make
• Its reverse actions to exocytosis. A pocket that cell can be taken by the cell its selfe.
• Its include that the " cellular" or cellular drinking by receptor

Phagocytosis

• Cells with a food parciles
• It is a lso a vacuol fuses hydrolity enzyme

Pinocytosis

• A droplets that cell contiously gets is has all and everthing.

Mediate endocytosis

• That enables and specific high substance on cell wall
• The receptors with the surface and the solute binds and goes a vesicle.
• Emptites from the cell and recycles.

Explores the role of CD4 and membrane proteins in HIV treatment. Discusses drugs like maraviroc and their mechanisms. Examines broader impacts of understanding membrane proteins on medical advancements and viral treatments.