Revision 1: Lipids, Proteins and Membrane Structure Flashcards
discuss PM components (excluding prot.s)
about 40% lipid, 60% protein, 1-10% cholesterol, 20% water
phospholipids: Head group is polar and made form variety of compunds eg choline, amine, AAs
- FA chain are most prevalently C16-18, unsat. side chain in cis formation leads to a kink that reduces packing
Plasmalogens: sphingomyelin: only phosph. that is not based on glycerol, but its conformation resembles other phosph.s
-glycolipids: sugar containing lipids, two types are cerebrosides (head group is a monomer) and gangliosides (head group is an oligosaccharide)
Cholesterol: makes up 45% of PM lipid
Lipid bilayer dynamics
1 Intra-chain rotation (ie. kink formation in the FA chains)
2 Fast axial rotation
3 Lateral diffusion w/in plane of bilayer
4 Flip-flop
Membrane prot.s: function, evidence, movement, periph/integ, asymmetry
Function: provides the distinctive functions of membranes eg enz.s, transporters, pumps, ion channels, receptors, energy transducers etc
Evidence: Functional: ion grad.s, facilitated diff., specificty of cell responses
-Biochemical: freeze frx, membrance fractionation and gel electrophoresis
Movement: rotation, lat. diffusion and conformational change
-Restricted by: lipid mediated effects (ie it tends to spearate out to fluid/chol. poor regions), PM prot. associations, extra-membranous (peripheral) prot.s (eg cytoskeleton)
The two types: Peripheral: bound to surface of membrances by electrostatic and H bonds, can be easily removed eg by changes in pH, ionic strength
-Integral: interacts w/ Hpho regions of lipid bilayer, needs agents to remove them eg detergents, organic solvents that compete for the non polar interactions in bilayer
Asymmetry: important for function, eg a receptor for insulin must have the recognition site pointing towards EC space
synthesis of prot.s, and how membrane prot. synth. specifically differs
general synth.: 1 free ribosome initiates prot. synth. from mRNA molecule
2 Hpho N terminal seq. formed
3 SRP binds to this signal seq.
4 Prot. synth. stops
5 GTP bound SRP directs ribosome synth. the secretory prot. to SRP receptor on cytosolic face of ER
6 SRP dissociates
7 prot. synth. continues and newly formed polypeptide is fed into ER via pore - the prot. translocation complex
8 signal peptidase cleaves the signal seq. once prot. is synth.
9 ribosome diss. and is recycled
Membrane prot. synth.: when it is translated, the ribosome finds a highly Hpho stop transfer signal about 18-20 AAs long (ie. the distance to cross the phosph. bilayer), the Hpho region remains in the ER membrane and the rest of the prot. is translated into the cytoplasm
unsat. FA’s effects on membrane fluidity
unsat. FAs have a kink that reduces packing between phosph.s -> inc.s membrane fluidity
explain the meaning of ‘fluid mosaic’
fluid: Hpho. integral components eg lipids and memb. prot.s move lat. throughout membrane
mosaic: made of many diff. parts eg glycoprot.s, integral prot.s, glycoprot.s etc
describe structure of cytoskeleton
composed of spectrin and actin fibres
each spectrin/actin fibre winds round another spectrin/actin fibre -> heterodimer, one heterodimer of each type then join at the ends to form an heterotetramer
attached to memb. by adapter prot.s glycophorin A (->Band 4.1) and Ankyrin (-> Band 3) on the PM
describe haemolytic anaemias
deficiency in a RBC’s cytoskeleton
Spherocytosis: spectrin is depleted by about 40-50%, inc. rounding up and lysis leads to dec. lifespan of RBCs
Elliptocytosis: spectrin is unable to form heterotetramers -> fragile elliptoid cells
cholesterol’s effects on membrane fluidity
chol. stabilises PM by H bonding to FA chains, abolishing endothermic phase transition of phosph. bilayers
The role of cholesterol is to stabilise membrane structure to prevent extremes of crystallisation or fluidity.
Intercalation of the rigid planar conjugated ring structure reduces phospholipid packing and therefore increases fluidity
Conversely, the rigid conjugated ring structure reduces phospholipid aliphatic tail mobility, so reducing fluidity.
how can a protein interact with the hydrophobic portion of a PM?
Transmembrane sequence of approximately 20-22 amino acids with hydrophobic R-groups (often folded into alpha-helical structure, could be multiple alpha-helices or rolled-up beta-sheet, e.g. bacterial porins)
Lipid-linked proteins through the insertion of the hydrophobic lipid moiety (e.g. post-translational modification with fatty acid (palmitoylation, mystriolation), e.g. G-proteins) )
Insertion of amphipathic alpha-helix from cytoplasmic side
