Cell Membranes Flashcards
What are the functions of the plasma membrane?
- Physical barrier, structural support & protection
- Transport - selective permeability
- Organelle delineation and individuality
- Cell recognition - intercellular communication - signal transduction
What is the basic structure of phospholipids?
- Backbone molecule
- 1 or 2 fatty acid chains (hydrophobic)
- Phosphate group
- Mar or may not have alcohol containing group
- They are amphipathic molecules
What is the structure of Glycerophosopholipids?
- Glycerol backbone
- 2 fatty acids at C1 & C2 - can be saturated or unsaturated
- Phosphate group at C3
- No alcohol containing group (But serine, choline or ethanolamine can be added to phosphate group)
What are Phospholipases (PLs)?
- Enzyme that cleaves bonds in glycerophospholipids
- PLC, PLD hydrolyse either side of the polar head (releasing glycerol backbone and OH- containing group respectively)
- PL(A1), PL(A2) hydrolyse FA from C1 and C2 respectively
- PLs are poisonous signals in venom: Phospholipase (A2) in venom causes relate of FA at C2 ultimately breaks down phospholipids (i.e. the membrane)
What is the structure of sphingolipids?
- Sphingosine backbone
- Single fatty acid chain attached at amino group
- MIGHT have phosphate and/or alcohol group
- Ceramides are simplest sphingolipids (1 FA linked at amide terminal)
What is the structure of Sphingosine?
- The backbone of sphingolipids
- Has amino group at C2
- Unsaturated 18C hydrocarbon chain
What is sphingomyelin?
- Sphingolipid found in the membrane bilayer of nerve cells
- Phosphate + choline group (Phosphocholine) attached to C of amide group
What are glycolipids?
- Part of sphingolipid family
- Ceramide bound to 1 or more sugar residue in glycosidic linkage
- Found in outer portion of cell membrane bilayer
Asymmetry and heterogeneity of membrane bilayer
2 leaflets (outside and inside) of membrane bilayer are NOT structurally or functionally identical.
Transverse Asymmetry of the membrane bilayer
Refers to different lipid and/or protein compositions in the 2 leaflets of a bilayer membrane
Later Heterogeneity of the membrane bilayer
Refers to different lipid and/or protein compositions in the plane of one of the leaflets of the membrane
3 Process that modulate membrane lipid movement
- Lateral Diffusion:
a. Lipid changes orientation within same plane of membrane
b. Heads still associating with heads etc.
c. Isn’t a lot of resistance to movement through the plane, therefore quite fast - Rotation:
a. Phospholipid rotates on axis to associate with neighbors
b. Stays in same spot so not a lot of resistance so quite fast - Transverse diffusion: (flip-flop)
a. From 1 leaflet to the other
b. Entire polar head and hydrophobic tail need to go through the membrane to get to the other side
c. Lots of resistance so its quite slow
3 Lipid-translocator proteins
- ATP-dependent flippases:
a. Transport lipids from outer leaflet to inner leaflet
b. E.g. (lipids that are transported)phosphatidylserine and phosphatidylethanolamine.
c. Needs to be input of energy (ATP) to break through resistance.
- ATP-floppases:
a. Transport lipids from inner leaflet to outer leaflet
b. E.g. (lipids that are transported) cholesterol, phosphatidylcholine and sphingomyelin. - ATP-independent bi-directional scramblases:
a. Moves lipids between bilayers.
b. Calcium driven
c. E.g. any lipid
What are Lipid rafts
- Subdomains of the plasma membrane that contain high conc. of lipids (esp. cholesterol and mostly saturated phospholipids) and proteins.
- Ordered and tightly packed, reduced fluidity.
- Function:
o Serves to concentrate molecules to aid in cellular processes such as cell signaling, signal transduction, protein trafficking.
Functions of membrane proteins
- Transport
- Enzymatic activity
- Signal transduction
- Cell-cell recognition
- Intercellular joining (synapses between neurons)
- Attachment
What are the 3 classes of membrane proteins?
- Integral membrane proteins – span entire width (or just 1 side) of membrane
- Peripheral protein – only on surface of membrane bilayer
- Lipid-anchored protein – protein attached to lipid, lipid inserted into membrane bilayer.
What are integral polytropic proteins?
Transmembrane proteins that span the entire width of the membrane
What are integral mono tropic proteins?
Integral proteins that are attached to 1 side of the bilayer but don’t span the entire width
What are alpha-helices?
Single stranded hydrophobic amino acids that for a helix and cross the membrane
Need 21-25 amino acids to cross the membrane
How do alpha-helices affect the fluidity of the membrane?
- α – helix kinks due to proline provides fluidity
- Membrane helix distortions are kinks at proline residues.
- Proline amino acid distorts the helix
- Proline can’t form H-bonds, this creates steric hindrance which also affects its neighbor blocking it from creating H-bonds.
What is a Hydropathy (Hydrophobicity) plot?
- Used to determine if an unknown protein is a membrane protein or not
What is glycophorin?
A glycoprotein on red blood cells made of a single alpha-helical TM-segment protein.
What is the glucose transporter?
A 12 spiral transmembrane alpha-helical segment which functions in transporting glucose across the plasma membrane
What are beta-sheets?
- found in membranes of bacterial cells
- Arranged in anti-parallel fashion
- Strands form zig-zag (3 strands)
- Multiple B-sheets in membrane come together to make a barrel. Need at least 9-11 amino acids per sheet to cross the membrane
- Hydrophobic amino acids orient toward the exterior (where they contact the surrounding lipids In membrane), and hydrophilic amino acids orient toward the aqueous interior pore.
What are porins?
- Type of beta-sheet found in the outer membrane of bacteria
- Acts as a pore through which mols can diffuse - polar residues face inside creating a hydrophilic channel
- Each porin has exclusion limits
What are the advantages of beta-sheets over alpha-helices?
- Alpha-helices require 21-25 residues (amino acids) to cross plasma membrane
- Beta-strand requires only 9-11 residues to cross plasma membrane
- Thus, with B-strands, a given amount of genetic material can encode a larger number of transmembrane segments.
- Bacteria prefer B-strands because they have less genetic information.
What are the 4 interactions of peripheral proteins with the membrane?
- Association with integral protein (integral protein embeds in bilayer)
- Amphipathic a-helix adheres to bilayer
- Hydrophobic loop. Hydrophobic amino acids loop into bilayer and associate with lipids.
- Ionic and H-bond interactions
What are the 4 linkages that link lipids to proteins in lipid-linked membrane proteins?
- N-Myristoylation
- S-Palmitoylation
- Prenylated anchors
- GPI anchors
What is N-Myristoylation?
- Protein-Lipid linkage in Lipid-linked membrane proteins
- FA is always Myristic Acid (14:0)
- FA is in membrane bilayer
- Myristic acid forms amide linkage with glycine amino acid in protein at N terminal
S-Palmitoylation
- Protein-Lipid linkage in Lipid-linked membrane proteins
- Palmitic acid (16:0) linked via ester linkage to -SH- group of cysteine residue of protein
- Protein can be released by hydrolysing ester linkage.
- Serine, threonine residues also linked (but less commonly than cysteine) and lipids (palmitic, myristic, steric acids) can also be used.
Prenylated Anchors
- Protein-Lipid linkage in Lipid-linked membrane proteins
- Linkage of prenyl groups – farnesyl (15C:3) and geranylgeranyl (20C:4) to carboxyl terminal cysteine of proteins.
- Linked in CaaX sequence:
o C – Cysteine to be prenylated to FA (farnesyl or geranylgeranyl)
o aa – 2 aliphatic amino acids
o X – amino acid determes enzyme specificity (farnesyl or geranylgeranyl)
If X = Ala, Met, Ser, or Gln ; protein with be farnesylated
If X = Leu; protein will be geranylgeranylated.
What are the 4 types of transport across biological membranes?
- Passive Diffusion
- Facilitated diffusion
- Primary Active transport
- Secondary active transport
What is Passive Diffusion?
Energy-indépendant process whereby small uncharged molecules (like H2O) travel down a concentration gradient
What is Facilitated Diffusion?
Energy-indépendant process whereby large polar molecules travel down a concentration gradient with the aid of integral membrane proteins
Action of the Glucose transporter
- Glucose binds to transporter protein that has binding site open to outside of cell.
- Glucose binding causes transporter to shift to its T2 config with binding site open to inside of cell
- Glucose released to interior of cell, initiating second conformational change in transporter
- Loss of bound glucose causes transporter to return to original (T1) conformation, ready for a further transport cycle.
What is Primary active transport?
Energy-dependant movement of molecules against a concentration gradient (e.g. Na/K Pump)
Action of the Sodium/Potassium pump
- Na+ high on outside of cell, K+ is low on outside (opposite on inside)
- Each cycle transports out 3 Na+ mols and 2K+ mols in.
- Open on intracellular site, with 3 Na+ binding sites
- Cytoplasmic Na+ binds to the sodium-phosphate pump
- Na+ binding stimulates phosphorylation by ATP
- Phosphorylation causes the protein to change its conformation, expelling Na+ to the outside
- Extracellular K+ binds to protein, triggering release of the phosphate group (back to ATP)
- Loss of phosphate restores the proteins original conformation
- K+ is released and Na+ sites are receptive again. Cycle repeats.
What is secondary activate transport (co-transport)?
- Na2+ is needed back in the cell, moves WITH conc gradient
o Energy is released - Energy release increases affinity for Glucose binding
- Glucose is bound and released inside cell against its conc. gradient
- The electrochemical energy released from Na moving down gradient co-transports glucose against its gradient.
- 2 types of these proteins:
o Antiporters: 2 mols go in different directions
o Symporters: 2 mols going in the same direction
