Membrane Proteins

Integral Membrane Proteins Properties

• Penetrate/pass through lipid bilayer

• Contain 1 or more hydrophobic regions embedded into the membrane

• A hydrophobic alpha helix is common secondary structure that spans the membrane

  • Held in place by van der Waals interaction between hydrophobic residues and lipids and ionic interaction with polar head groups

  • Tail of the helix will have positive a.a on the cytosolic side to associate with polar head

  • Mostly comprised of hydrophobic a.a

• Helix roughly spans 20-30 a.a long

IMP Function

• Function as

  • Transporters: move ions/solute across membrane

  • Anchors: binding intra- or extra- cellular components to the membrane

  • Receptors: binding ligands to initiate signal transduction apthways

  • Enzymes: can catalyzed reactions both intracellular and exoplasmic side of membrane

  • Electron transporter: transfer electrons during photosynthesis and respiration

Transmembrane Proteins (type of IMP

• Can have multiple membrane spanning alpha-helices

• Helices are connected by helical loops

• Bacteriorhodopsin is connected by non-helical loops at the inner and outer face of the membrane

• Hydrophobic interaction between non-polar a.a and fatty acyl groups of lipids anchor the protein

• 7 helices are clustered together but not exactly perpendicular to bilayer to provide a proton pathway

Beta Barrels

• Can form different number of beta strands

• Abundant on outer membranes of gram negative bacterioa, mitochondria and chloroplast

• Allows passage of small hydrophilic molecules

• Nonpolar a.a facing the fatty acyl of lipids and polar a.a facing the lumen of barrel

Peripheral Proteins

• Located entirely outside of bilayer on either the extracellular or cytoplasmic side

Lipid Anchored Membrane Proteins

• Located outside the membrane but covalently anchored to a membrane protein

• Protein is attached to the cytosolic side by

  • Covalently attach fatty acid chain (Acylation)

    • C-term in cytosol

  • Prenyl group (prenylation)

    • N term in cytosol

    • Connected to a cysteine

  • Protein is synthesized in cytosol since it is soluble

• Proteins attached to the noncytosolic side by an oligosaccharide linker to phosphatidylinositol

  • GPI anchor

  • Glycosylphosphatidylinositol

  • Its attached to proteins in the lumen in the ER

  • Always on ECF

Peripheral Membrane Proteins

• Doesn't interact with hydrophobic core of lipid bilayer

• Associates with membrane through interactions with IMP or lipids polar hear groups

• Can be readily removed from membranes by changes in pH and ionic strength

 

Most plasma membrane proteins are glycosylated and face the exoplasmic domain

Why is membrane fluidity important

Function of membrane is dependent on its fluidity

• Vesicle formation, fusion, secretion

• Cell division

• Muscle contraction

• Cell migration

• Signaling mechanisms

WIll only function in a fluid state

Transition temperature

• The temperature at which it become fluid

• Phase transition is the change of states

• Anything below Tm would disrupt membrane fluidity and function

• Tm is dependent on lipid composition of the membrane

Factors that affect TM

• Length of fatty acid tails

  • Fluidity increase with shorter carbon tails, Decrease Tm

  • Fluidity decrease with longer tails, Increase Tm

    • More carbons = more van der waals interactions

• Saturation

  • Saturated fatty acids pack together, increase Tm

  • Unsaturated fatty acids have double bonds that causes a bend in the chain preventing proper packing. It will decrease Tm, cause membrane to be fluid at a lower temperature

• Cholesterol

  • Stabilize and maintain membrane

  • Decreases permeability of membrane to ions and small polar molecules

    • Cholesterol fills the space between hydrocarbon chains of phospholipids, blocks routes that ions/small molecules can take through the membrane

  • Acts as a fluidity buffer

    • Decrease fluidity with unsaturated fatty acids, packs the space that double bonds cause

    • Increase fluidity with saturated fatty acids, causes there to be space between fatty acids

Maintain membrane fluidity

• Cells have enzymes that alter fatty acids in response to need

• Cells can regulate lipid composition to maintain constant membrane fluidity

Nature and Function of a lipid raft

• Localized regions of membrane lipids in association with specific proteins

• Change composition as lipids and proteins move in and out of them

• Elevated levels of cholesterol and sphingolipids

• Sphingolipids have longer and more saturated fatty acids

• 1-2 nm thicket and less fluid than rest of membrane

• Structures server as floating platforms that concentrate proteins into compartment on the membrane

• Role in detecting and responding to extracellular signals

Dynamic Nature of Plasma Membrane

• Lipids are mobile within their monolayer

• Rotation of about axes can occur

• Can perform lateral diffusion fast

• Movements are rapid and random

• To flip flop, hydrophilic head must pass through hydrophobic sheet of membrane

  • Flippases are enzymes that move phospholipids

Type of Mobility in membrane Protein

• Random movement

• Immobile (intracellular tethering)

• Directed Movement

• Reduced Mobility (crowding from other proteins)

• Fenced or Corralled

• Extracellular entanglement

FRAP

• Fluorescence recovery about photobleaching

• Label proteins with fluorescence dye

• Use a laser beam to bleach the area

• Record the time it takes for fluorescent-labeled molecules diffuse into the bleached area

• Proteins move slower in living cell membrane

• Mobility of many proteins are limited