Lecture 4: Specialized membrane proteins Flashcards
What are the two types of cell membrane proteins?
Integral membrane proteins
Peripheral membrane proteins
Integral membrane proteins
Integral membrane proteins are associated with one or both layers of the
lipid bilayer membranes
Peripheral membrane proteins
associated peripherally with the cell membrane
How are integral membrane proteins associated to the membrane?
One of the lipid bilayers with a covalent lipid linker
One of the lipid bilayer with a non-covalent lipid linker
Or with an integral protein
Functions of membrane proteins
Pores: to allow passage of metabolites or nutrients.
Ion channels: for intake and output of electrolytes.
Transporters: to allow the movement (entry and exit) of molecules Enzymes: to catalyze reactions.
Receptors: to receive and propagate signals.
Cell adhesion proteins: to connect cells for cellular communications.
Structural proteins: to give mechanical properties to cells.
What are defects in the function of membrane proteins associated with?
Diseases
Why are integral membrane proteins difficult to purify?
They have significant hydrophobic regions designed to interact with the lipid membrane bilayer.
What types of secondary structures do integral membrane proteins have?
Alpha helical (coiled) and beta sheets
Most integral membrane proteins use one or more alpha sheets. But the can also form beta pleated barrels
What does polytonic mean?
Transmembrane, span entire membrane
What does monotonic mean?
Integral protein that only associates with one leaflet of the bilayer
How do monotonic integral membrane proteins interact with the membrane?
- amphipathic alpha helix
- hydrophobic loops
- a covalently attached lipid group
- electrostatic or ionic interactions with membrane phospholipids
See figure
Specific functions of integral membrane proteins
allow cells to interact with and communicate with their environment.
gatekeepers of the cell — entry and exit route for ions, nutrients, waste products, and proteins.
Receive and transmit signals from both long range (hormones, growth signals) and short range (cell: cell communication)
Transport of small molecules and inorganic ions across the membrane
See table
What is facilitated diffusion?
passive movement of molecules/substrates across the cell membrane by a carrier/transporter protein that does not require an external energy source (i.e. metabolic energy/ATP) directly or indirectly.
What molecules use facilitated diffusion?
Water soluble molecules (ex: glucose)
Which way does substrate move in facilitated diffusion?
Down the concentration gradient
What type of proteins does facilitated diffusion require?
Integral transmembrane proteins
What kind of interaction occurs between the solute and the carrier in facilitated diffusion?
substrate has to bind specifically and non-covalently to the carrier
Rate of diffusion during facilitated diffusion
carrier is saturable; and the rate of diffusion is directly proportional to the concentration gradient.
How can glucose carriers be inhibited?
Glucose analogs
How are glucose transporter isoforms different from each other?
Where they are located
Affinity for glucose may differ
Activity may depend on insulin
Regulation of GLUT4 in membrane
In the absence of insulin, the GLUT4 transporters are located inthe intracellular vesicles just inside the plasma membrane
In the presence of insulin, it binds to the insulin receptor and initiates a signal transduction cascade; one result from this cascade is that the GLUT4 containing vesicles fuse with the plasma membrane, allowing it to function.
Clinical implications of GLUT4
A mutation at amino acid position 383 has been found in a small number of patients with non-insulin dependent diabetes
A fungal mycotoxin, cytochalasin B, can inhibit both GLUT1 and GLUT4 (among other affects)
Indinavir, an HIV protease inhibitor, is also an inhibitor of GLUT4, leading to metabolic side effects seen in many patients taking this dru
What is the sodium-glucose symport essential for?
sodium dependent glucose transport in the apical membrane of the small intestine (SGLT1) or the apical membranes in the proximal tubules of the kidney (primarily SGLT2, small amount of SGLT1)
What do sodium- glucose symports need to function?
require the Na+ gradient generated by the Na+-K+-ATPase on the basolateral membrane
Efficiency of sodium-glucose symports
extremely efficient transporters
100% of the glucose filtered in the kidney is reabsorbed from the filtrate via sodium co-transport
A model for sugar transport across the enterocyte showing the brush-border SGLT1 and GLUT5 transporters and the basolateral Na+-K+-pumps and sugar transporter GLUT2.
See figure
2 types of glucose transporters working in concert
What causes defects in SLC5A1?
congenital glucose/galactose malabsorption (GGM)
characterized in the first few weeks of life in infants by severe diarrhea and dehydration, which are usually fatal unless glucose and galactose are eliminated from the diet.
How should diarrhea be treated?
Oral rehydration therapy with solutions of glucose and salt is an extremely important treatment for acute diarrhea (esp. with cholera)
Glucose and sodium are transported into the enterocytes and then to the blood stream; water follows by osmosis, leading to rehydration
What is essential for the functioning of transport proteins?
Conformational changes
