MEMBRANE PROTEINS Flashcards
How to membrane proteins interact with the membrane?
- Single and multiple pass alpha helix, integral membrane proteins, can also be lipid anchored
- Rolled up beta sheets, forming pores
- Anchored by an amphiphilic alpha helix
- Association via non-covalent interaction with a bona fide membrane protein `
What are lipid anchors?
Long chain fatty acids and a cholesterol intermediate which allows a protein to attach
- Longer chain=more stable
- All are reversible by proteolysis (de-esterification) and lipid transferase
- Can be used to recruit proteins to, or detach proteins from the membrane
- Lipid anchored proteins are located on the surface of the cell membrane that are covalently attached to lipids embedded within the cell membrane. These proteins insert and assume a place in the bilayer structure of the membrane alongside the similar fatty acid tails
What do most eukaryotic integral membrane proteins cross the membrane as?
Alpha helices
-Transmembrane a-helices are enriched in non-polar amino acids (hydrophobic)
What are the characteristics of extracellular domains?
They are often glycosylated and have disulphide bonds
What consists of the protective carbohydrate layer of the cell?
Glycoproteins and glycolipids
What are the characteristics of integral proteins?
- Diffuses laterally
- Can change conformation
- Can be internalized and recycled
- Lipid anchored proteins can associate/dissociate from the membrane without changing conformation
What are integral proteins?
These are embedded within the plasma and have a range of functions
-It embeds by regions of specific amino acids which are attracted to the middle of the plasma membrane.
What are the functions of membrane proteins?
- Channels (CFTR, a chloride channel, mutation leads to cystic fibrosis)
- Transporters (ABCB1, drug efflux pump, causes multidrug resistance)
- Anchors (Connexin 26, adherens gap junction between cochlear cells, allows ion flow and electrical impulse to flow)
- Receptors (FGFR3+FGF, tyrosine receptor kinase (MAPK), changes gene expression, decreases proliferation of bone cells, mutations causes achondroplasia)
- Enzymes (Phospholipase C, a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group, signal transduction pathways)
How do channels mediate passive movement of solutes?
- It is a continuous pore through the membrane
- Can be regulated
- Selective
- Only allows solutes to move down its electrochemical gradient to equilibrium
- Allows passive flux from a high to low concentration
- Opened and closed by voltage changes
- High bulk flow
How do transporters facilitate passive movement of solutes?
- Specific solute binding sites alternatively exposed on different sides of the membrane
- Solute binding induces a conformational change, exposing the solute to other sides of the membrane
- Allows movement down electrochemical gradient
What is the difference between passive and active transport?
Active transport is against the concentration gradient through the use of ATP
- High affinity solute binding site exposed to cytosol
- Solute binding induces ATP binding/lysis
- Conformational changes exposes low affinity binding site to extracellular space
- Net flux dependent on ATP (primary active pump)
What are electrochemical gradients?
An electrochemical gradient is a gradient of electrochemical potential, usually for an ion that can move across a membrane. The gradient consists of two parts, the CHEMICAL gradient, or difference in solute concentration across a membrane, and the ELECTRICAL gradient, or difference in charge across a membrane
- Pertinent to the human neuronal plasma membrane
- Membrane potential (voltage difference) is -70mV
- Efflux of Na by the Na/K ATPase pump
- Negative charge on the inner leaflet phosphatidylserine
- Electrochemical gradient for Na+ allows for action potential to occur `
How is transport driven using the energy from ion gradients?
- Strict coupling of the binding of solute and co-transported ion
- Energy released as co-transported ion moves down its electrochemical gradient drives the solute up its conc gradient
- Can by SYMPORT (in the same direction) or in the opposite direction (antiport)
- Generated by an ATP driven pump, secondary active transport
What is difference between primary and secondary active transport?
Primary transport is through ATP hydrolysis while secondary transport is through an ion gradient
PRIMARY:
-Moving against conc gradient is possible if coupled to ATP hydrolysis (eg. Na+/K+ ATPase, SERCA: sarcoplasmic endoplasmic reticulum Ca2+ P-type ATPase transporter)
SECONDARY:
-Moving against conc gradient is possible if coupled with downhill (with conc gradient) movement of an ion 9eg. SGLT1: sodium glucose linked transporter of intestinal epithelium, Na+ driven glucose transport)
How to cell membranes facilitate the passage of polar molecules (ions, sugars and amino acids)?
The plasma membrane is selectively permeable
- Hydrophobic molecules and small polar molecules can diffuse through the lipid layer
- Large polar ions cannot diffuse through, integral membrane proteins enable them to pass by active or passive transport
