Membrane Proteins

How are lipid anchored protein and peripheral membrane proteins similar?

They are both water soluble proteins lacking appreciable hydrophobic character

beta barrel transmembrane protein

a beta barrel is formed from an antiparallel beta pleated sheet, with hydrophobic amino acids facing the fatty acid tails of the membrane and the hydrophilic amino acid side chains facing the interior water filled pore

detergent

a water-soluble cleaner that can emulsify dirt and oil

sandwich model

an early model of how membranes were structured where it was thought the phospholipid layer was in between proteins

What are the functions of lipid anchored proteins?

cell communication, pathogen entry

Provide examples of the types of proteins that fall into the integral membrane protein category:

cell surface receptors, glycoproteins, transmembrane anchors, channels, pores, transport proteins

cell surface receptor

cell-surface protein that transmits a signal from the exterior of the cell to the interior, even though the ligand does not enter the cell

What are the functions of amphipathic alpha helical transmembrane proteins?

proteins with this type of secondary structure can form water filled channels in the membrane so long as they are at least 3 alpha helices coming together to form the channel. The hydrophobic sides of each helix face the fatty acid tails of the membrane and the polar/charged sides of each helix face the interior water filled channel. These channels allow water soluble ions to pass through the membrane

What are the functions of hydrophobic alpha helical transmembrane proteins?

proteins with this type of secondary structure function as receptors, transmembrane anchors, transport proteins. These are proteins that are embedded into the membrane but do not function as pore/channels.

What are the functions of peripheral membrane proteins?

regulation of cell signaling, regulation of membrane bound enzymes

beta-barrel

interior is polar and allows water and small polar molecules to pass through the membrane

integral membrane protein

proteins that span the membrane and have segments facing both the interior and the exterior surfaces

hydrophobic alpha helix transmembrane protein

proteins with hydrophobic alpha helical transmembrane domains; the 20-30 amino acids that span the membrane form an alpha helix, with the hydrophobic side chains facing the fatty acid tails

What are the functions of beta barrel transmembrane proteins?

proteins with this secondary structure form large water filled pores in the membrane with their hydrophobic amino acids facing the fatty acid tails of the membrane and the polar/charged amino acids facing the interior of a large water filled pore. These pores allow larger polar/charged molecules to pass through the membrane

How do you "dissolve" the membrane and associated proteins so they are water soluble?

Add detergent if the protein is an integral membrane protein or lipid anchored protein because you must solubilize the membrane components to solubilize the proteins. The integral membrane protein has hydrophobic stretches that must be part of detergent micelles and the lipid anchored protein has hydrophobic "liquid parts" that must be included in a detergent micelle.

What does it mean to be an "amphipathic" protein and what does it have to do with being a membrane protein?

An amphipathic protein has stretches of non polar amino acids (long enough to span a lipid bilayer) flanked by polar/charged amino acids. The non polar region of the protein spans that membrane with its non polar amino acid side chains interacting chemically with the fatty acid tails of the membrane and the polar/charged amino acids are on the outside of the membrane.

alpha helix

A spiral shape constituting one form of the secondary structure of proteins, arising from a specific hydrogen-bonding structure.

lipid anchored protein

A type of integral membrane protein that is attached to the membrane via a lipid molecule.

amphipathic alpha helix

Hydrophobic face outward and interact with membrane. Polar solute interacts with polar face and forms lumen. Distribute R-groups accordingly.

How would you isolate a peripheral membrane protein from the membrane? Would you need a detergent?

No detergent needed... just break open cells, add salt (like NaCl), spin down membranes in centrifuge and the peripheral membrane protein will be released from the membrane. Membranes will pellet to the bottom of the tube, peripheral membrane protein will be in aqeuous supernatant.

What does it mean to be "associated" with the membrane?

A membrane protein can interact with the membrane in many ways, not necessarily by being "embedded" in the membrane. Proteins can stick to the outside of the membrane (to the polar/charged head groups of the bilayer) without any contact with the interior of the membrane at all or they can be "stuck" to the membrane by having a covalently attached fatty acid or lipid which inserts into the bilayer. All proteins that are in contact with the bilayer, no matter how they do it, are "membrane associated"

peripheral membrane protein

A protein that is associated with the plasma membrane of a cell, but that is not embedded in the lipid bilayer. Peripheral proteins typically associate with embedded proteins through hydrogen bonding or electrostatic interactions.

glycoprotein

A protein with one or more carbohydrates covalently attached to it.

Describe how lipid anchored proteins associate with membranes

Lipid anchored proteins are "water soluble" proteins which have a covalently linked lipid or fatty acid. The lipid or fatty acid part of the lipid anchored protein inserts into the membrane and interacts with the fatty acid tails of the membrane.

How are lipid anchored protein and peripheral membrane proteins different?

Lipid anchored proteins have a covalently bonded fatty acid (fatty acid modified proteins) or phospholipid (GPI anchored proteins) that inserts into the phospholipid bilayer and anchors the protein in the membrane

What distinguishes an integral membrane protein from the other two?

Some portion of the integral membrane proteins directly interacts with the fatty acid tails of the membrane. Thus, the integral membrane protein is embedded in the phospholipid bilayer. Lipid anchored proteins (the protein parts) and peripheral membrane proteins do not interact with the interior of the membrane.

fluid mosaic model

The currently accepted model of cell membrane structure, which envisions the membrane as a mosaic of individually inserted protein molecules drifting laterally in a fluid bilayer of phospholipids.

What sort of chemical interactions or bonding is responsible for the interaction of a peripheral membrane protein with the membrane?

electrostatic (hydrogen bonding, ionic bonding)

polytopic

having a polypeptide chain that traverses the membrane once or several times

Amphipathic

having both a hydrophilic region and a hydrophobic region

amphipathic alpha helix transmembrane protein

in this case, the alpha helical transmembrane has alternating polar/charged and non polar amino acids so that the amino acids on the side of the helix in contact with the fatty acid tails are non polar and the amino acids on the side of the helix that will face the water filled pore are polar/charged

What three general categories of membrane proteins are we talking about in this class?

integral membrane proteins, lipid anchored proteins, peripheral membrane proteins