Final: Chapter 9 - Membrane Structure Flashcards
What are the two main functions of a membrane?
1) Define inside and outside of the cell or organelle
2) Control permeability of ions and small molecules
What are membranes primarily composed of?
lipids and proteins
What are three common lipids that are found in cell membranes?
Glycerophospholipids, sphingolipids, and sterols
What percentage of protein content in membranes?
15-80%
What is the purpose of proteins in cell membranes?
to add function
What are the three types of proteins based on their association with a membrane?
1) Peripheral 2) Integral 3) Lipid-anchored
What is a peripheral membrane protein?
One that does not penetrate the lipid bilayer and is mainly associated to the polar groups on the exterior of the membrane via H-bonds and ionic bonds
What is an integral membrane protein?
One that penetrates into or through the lipid bilayer, associating with the hydrophobic interior with its own hydrophobic portions
What is a lipid-anchored membrane protein?
One that covalently linked to lipids in the membrane
How is a peripheral protein cleaved from a membrane?
Change in pH or salt concentration
How is an integral protein cleaved from a membrane?
A nonpolar solvent or detergent must be used to break apart the membrane
How is a lipid-anchored protein cleaved from a membrane?
Must selectively cleave protein or destroy membrane to release it
What is the fluid mosaic model?
describes how membranes are composed of a dynamic and fluid lipid bilayer containing a diverse array of proteins and molecules that move around within the membrane
Describe the structure of an integral membrane protein
The membrane spanning portion is dominated by alpha-helices and beta-sheets
What are two reasons that alpha-helices and beta-sheets are more favorable in the lipid bilayer?
1) They are stabilized by H-bonds between AAs and their backbone which prevents interactions with the non-polar inner lipid bilayer
2) alpha-helices are primarily composed of nonpolar amino acids
What does a negative hydropathic index value signify?
The AA is hydrophilic (polar)
Whay does a positive hydropathic index value signify?
The AA is hydrophobic (nonpolar)
Do transmembrane protein domains exhibit a negative or positive hydropathic index overall?
Positive
Do extracellular and intercellular protein domains exhibit a negative or positive hydropathic index overall?
Negative
What is a beta-barrel?
A pore in the cell membrane formed by beta-sheets
Describe AA orientation in a beta-barrel?
Nonpolar AAs point outwards and face the lipid bilayer
Polar AAs point towards the center of the pore
Name 3 characteristics that most membranes have?
1) transverse asymmetry
2) lateral heterogeneity
3) lipid movements
What is transverse asymmetry?
the two leaflets of a lipid bilayer have different lipid compositions
What is lateral heterogeneity?
particular lipids or proteins cluster together within the membrane
What is anti-gauche isomerization?
Switch from gauche arrangement (where bulky groups are positioned at a 60-degree angle to each other) to an anti arrangement (where the bulky groups are positioned directly opposite each other at a 180 degree angle)
What is an undulation?
membrane movements up down in a wave like motion
What kind of lipid movement do proteins typically assist with?
Flip-flop
Why are flip-flop proteins necessary?
To maintain transverse symmetry
How is protein assisted lipid movement powered and why?
using free energy from ATP hydrolysis because energy is required to move polar heads across the nonpolar bilayers
What is flippase?
A protein that assists in lipid flipflop movement from outside the cell to in
What is floppase?
A protein that assists in lipid flipflop movement from inside the cell to outside
What is scramblase?
A protein that assists in lipid flipflop movement into the cell and out of the cell
Why is remodeling and curvature of membranes necessary?
For cell division, endocytosis, and exocytosis
What five ways membranes can be remodeled and curved?
1) changing lipid composition or head group composition
2) Addition of membrane proteins
3) Amphipathic helix insertion
4) Scaffolding
5) Cytoskeleton pushing or pulling of the membrane
How do membrane proteins and amphipathic helix insertion cause membrane curvature?
Causes one leaflet to be longer than the other
How do scaffolding proteins cause membrane curvature?
Interacts with polar head groups of membrane and enforce curvature with protein structure
What are two reoccurring themes of membrane transport?
1) concentration gradients
2) transport proteins to help facilitate
What are the three types of membrane transport?
1) passive diffusion
2) facilitated diffusion
3) active transport
What is passive diffusion?
When transported species are moved across the membrane in a thermodynamically favorable direction without the help of specific transport proteins
What kinds of molecules undergo passive transport and why?
nonpolar small molecules; can pass through hydrophobic layer and fit between lipids
In terms of concentrations, which direction to species move during passive diffusion?
high concentration to low concentration
What is facilitated diffusion?
transported species moves across membrane in a thermodynamically favorable direction with the help of specific transport protein
Describe proteins involved in facilitated diffusion?
commonly channel proteins that display an affinity or specificity for the transport molecule
How can facilitated diffusion be distinguished from passive diffusion experimentally?
by plotting saturation behavior (velocity vs concentration)
How can facilitated diffusion and passive diffusion be differentiated using a saturation curve?
- facilitated diffusion displays a square root function, indictive of saturation kinetics
- passive diffusion displays a linear relationship between
Why does facilitated diffusion experience saturation kinetics?
because its specificity implies a form of binding interactions; thus, the protein that facilitates diffusion can become saturated
What are four themes of channels involved in facilitated diffusion?
1) typically comprised of quaternary structure
2) Contain a selectivity filter
3) Can be gated
4) Width provides selectivity
Describe selectivity filters involved in facilitated channel diffusion?
commonly charged and use AAs to select for particular ions/molecules
What are the three kinds of gated channels?
1) voltage
2) ligand
3) pH
How does width of a channel affect selectivity?
Bigger channels allow more things through
In channel proteins, what are two typical arrangements of subunits to form quaternary structure?
1) arrange to form a central pore
2) each subunit has a functional pore
What form of transport do potassium channels utilize?
facilitated diffusion
What is the function of a potassium channel?
To move K+ ions from the interior of the cell to the exterior
Describe the quaternary and tertiary structure of a potassium channel?
Made of four subunits each containing a transmembrane alpha helix that form the central pore
Describe the nonselective portion of the pore in a potassium channel
about 10 angstroms wide and filled with water
How wide is a potassium channel selectivity filter?
3 angstroms wide
Why does the carbonyl backbone face the center of the pore in a potassium channel?
Provides four negatively charged oxygens per pentapeptide fragment that can interact with K+
Describe the peptide fragments that facilitate selectivity in potassium channels?
TVGYG fragments with their carbonyl backbone and one OH group (from T) facing the center of the pore
Why do potassium channels select for K+ over Na+?
Energy required to desolvate K+ as it enters the potassium channel is less than the energy released when the selectivity filter resolvates K+; is favorable
How is potassium channel direction reversed?
Reversing the K+ concentration gradient
How do gated potassium channels open and close?
They change between open and closed confirmations
What is active transport?
transported species moves across membrane in thermodynamically unfavorable direction with help of specific transport protein and energy input
What are three possible energy sources for active transport?
1) ATP
2) ion gradient
3) light
What are inhibitors of sodium pumps?
cardiotonic steroids
How do cardiotonic steroids inhibit sodium pumps?
They form a stable complex with E2-P confirmation, preventing phosphate hydrolysis necessary to return to E1 confirmation
How do cardiotonic steroids increase heart rate?
1) sodium pump in E2P causes K+ to accumulate in the cell
2) Opens voltage-gated calcium channels
3) Ca2+ accumulates in cell and triggers muscle contraction
Describe the structure of a cardiotonic steroid
Contains a common steroid core with a lactone ring attached at C17 and a Oh at C14
Why does K+ pass through potassium channels rapidly?
binding of additional K+ in the channel repels K+ that are currently in the channel
What kind of transport do sodium pumps exhibit?
active transport
What is the function of sodium pumps aka Na+/K+-ATPase?
To pump Na+ out of the cell and K+ into the cell using energy provided by ATP hydrolysis
Describe the main components of Na+/K+-ATPase structure
1) three unidentical subunits
2) Asp 369 that accepts a phosphate from ATP
3) lots of alpha helices because it is an integral membrane protein
What is an example of Na+/K+-ATPase inhibitor?
cardiotonic steroids
What are the three primary components of cardiotonic steroid structure?
1) common steroid core
2) lactone ring at C17
3) hydroxyl (OH) at C14
What is an ABC transporter?
An ATP binding cassette transporter
What is an example of a MDR pump?
ABC transporters
What are MDR pumps?
Multi-drug resistance pumps
What do MDR pumps do?
pump cellular waste and drugs out of the cell
What kinds of cells typically evolve MDR pumps? How do they evolve them?
bacterial and cancer cells; adaptation of pumps that typically expel cellular waste in response to drug stressors
Describe the structure of an ABC transporter?
Two transmembrane protein domains form a pore
Two nucleotide binding domains bind to and hydrolyze ATP
The domains can be part of the same polypeptide chains or different ones
What part of an ABC transporter functions as the ATP binding cassette?
nucleotide binding domains
What is secondary active transport?
Transport that uses energy from an ion gradient established by primary active transport
What is a common example of secondary active transport?
Na+ and H+ gradients transporting other molecules
What is a symporter?
A secondary active transporter in which ions and molecules move in the same direction
What is a antiporter?
A secondary active transporter in which ions and molecules move in opposite directions
In what organism is AcrB found?
E. coli
What kind of transport does AcrB undergo?
secondary active transport
What kind of secondary active transporter is AcrB?
A antiporter
Describe the structure of AcrB
composed of three identical subunits (homotrimer) that each have a pore
What powers transport of drug molecules through AcrB?
H+ moving with its gradient through the channel drives subunit confirmational changes
Describe the confirmational changes a subunit of AcrB undergoes as a drug molecule passes through it? (2 steps)
1) drug binds to subunit in L and triggers change to T
2) Confirmational change to O releases drug
What are the threes confirmations possible for a subunit of AcrB?
L - loosely bound to drug molecule
T - tightly bound to drug molecule
O - open, not bound to drug molecule
How do the subunits of AcrB interact?
cycle independently of one another
