Biological Membranes and Membrane Proteins (L13) Flashcards

1
Q

what are a great model for studying biological membranes, lipids, integral membrane proteins, and membrane skeleton?

A

RBCs

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2
Q

8 functions of biological membranes

A
  • compartmentalization
  • barrier to diffusion
  • define organelles and cell boundaries
  • scaffolds for proteins
  • transport molecules
  • transmit information
  • shape
  • assemble polysaccharides
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3
Q

general properties of membranes

A
  • fluidity
  • membrane fusion
  • selective permeability filter
  • capacitance
  • regulate information
  • asymmetry and scaffolding
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4
Q

what is capacitance function of membranes?

A

barrier to rapid transport of ions, electrical resistance, and charge difference - maintains 20-80 mV voltage (negative inside cell)

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5
Q

general composition of membranes

A
  • lipids
  • proteins
  • polysaccharides
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6
Q

what do lipids self-assemble into?

A
  • micelles
  • liposomes
  • bilayers
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7
Q

primary lipids in biomembranes?

A
  • phosphoglycerides
  • sphingolipids
  • cholesterol
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8
Q

importance of phosphoglycerides

A

important for compartment identity and precursors for signal transduction

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9
Q

defining part of a sphingolipid?

A

sphingosine - amino alcohol w/ long hydrocarbon tail

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10
Q

significance of plants having little cholesterol

A

promoted as heart healthy

  • could block/compete w/ other sterols for uptake
  • increase # of sterols in blood -> might signal for less cholesterol synthesis
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11
Q

cause of atherosclerosis

A

cholesterol, etc. accumulating on the inner walls of arteries and limiting blood flow and oxygen delivery to tissues

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12
Q

potential side effect of statins to lower cholesterol?

A

cholesterol is important precursor for vitamin D, bile acids, steroid hormones, cholesterol esters, modified proteins

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13
Q

how do proteins move around in the membrane?

A

mostly lateral movement - rarely flip flop (but flipases do that)

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14
Q

changes in membrane lipid composition that decrease freezing point

A
  • shorter chain length
  • more double bonds
  • less sterol
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15
Q

how does a decrease in freezing point affect fluidity?

A

minimizes the amount of interaction b/w FA’s -> increase fluidity

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16
Q

three types of membrane proteins

A
  • peripheral
  • lipid-anchored
  • integral or trans-membrane
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17
Q

integral membrane proteins

A

-have one or more transmembrane a-helix

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18
Q

what is the major membrane protein of RBCs?

A

glycophorin

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19
Q

lipid-anchored proteins

A

-associate via fatty acyl or prenyl groups

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20
Q

Ras

A

small G protein monomer - Tyr kinase signaling

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21
Q

Rabs

A

proteins that help specify compartment ID

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22
Q

peripheral proteins

A

-associate w/ integral membrane proteins or bind to phospholipid head groups

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23
Q

what type of proteins can be extracted ionically?

A

peripheral - extracted by salt treatments

24
Q

what type of proteins can only be extracted by detergents?

A

integral - detergent is a small amphipathic molecule that make micelles and remove integral proteins

25
ionic detergents
SDS (sodium dodeylsulfate) | sodium deoxycholate
26
non-ionic detergents
triton X-100 | octylglucoside
27
what are lipid rafts?
microdomains of specific lipids that cluster together and are different from surrounding lipids
28
components of lipid rafts
- no glycolipids, PE, PC - enriched w/ glycosphingolipids and cholesterol - enriched for acylated peripheral/integral proteins
29
6 functions of lipid rafts
1. signaling platforms 2. exocytosis 3. endocytosis 4. pathogen entry 5. apoptosis 6. cytoskeletal organization
30
functions of membrane fluidity
- response to temp change - fusion and fission/sealing damages - substrate exchange - ETC - multiprotein complex formation
31
evidence that proteins and lipids float in plane of membrane comes from....
- cell fusion experiments - FRAP - patching - lazer tweezers
32
FRAP
fluorescence recovery after photobleaching 1. label membrane proteins w/ fluorescent reagent 2. bleach with laser 3. observe fluorescence recovery (characteristic kinetics) can estimate diffusion constants and how much molecules move around
33
do all membrane proteins and lipids diffuse?
no
34
when can lipids and proteins be immobilized?
- if in lipid rafts (microdomain) - protein-ECM interaction - protein-membrane skeleton association - cell-cell interaction
35
describe membrane skeleton
non-covalent, submembranous array of proteins
36
functions of membrane skeleton
- MAINTAINS CELL SHAPE - stabilizes lipid bilayer - creates and stabilizes domains of integral membrane proteins - regulates exocytosis and membrane vesicle trafficking - provides sites of attachment for cytoskeleton
37
parts of membrane skeleton
- a and B spectrin - ankyrin - band 3 - glycophorin - band 4.1 - actin
38
function of Band 3
major integral membrane protein: HCO3-/Cl- antiporter - 20-25% of total protein - can be cross-linked to ankyrin
39
function of glycophorin
integral membrane protein - heavily glycosylated - negative charge keeps surface of RBC hydrophilic - keeps RBCs from sticking together (charge repulsion)
40
function of band 4.1
anchor for spectrin
41
what makes up junctional complex?
actin/spectrin binding with band 4.1
42
function of a and B spectrin
help RBC change shape
43
spectrin heterodimers
Bands 1 and 2 - 2 anti-parallel chains, w00 nm long - B-subunit, N-terminus associates w/ F-actin - modulated by CaM, phosphorylation, PIP2 - BINDS TO ANKYRIN AND BAND 4.1
44
function of actin in the RBC membrane skeleton
present only in small fragments - hub for spectrin molecules to associate to form a filamentous meshwork
45
hereditary spherocytosis mutations
can occur in several different genes: - a and B spectrin - protein 4.2 - band 3 MOST COMMON DEFECT = ANKYRIN results in small, spherical RBCs with increased fragility, decreases flexibility
46
what molecules are permeable, slightly permeable, impermeable through membrane
permeable: gases, small uncharged polar molecules slightly permeable: some small uncharged polar molecules (like urea) impermeable: large uncharged polar molecules, ions, charged polar molecules
47
three classes of transport integral membrane proteins
1. channels 2. transporters 3. pumps mediate transport of ions, sugars, aa's, and other metabolites across cellular membranes
48
pumps
active transport - couples movement of S against its concentration gradient to ATP hydrolysis ex: Na+/K+ pump
49
Na+/K+ pump
important plasma membrane protein | -Na out, K in (antiporter)
50
what drugs target Na+/K+ pumps?
ouabain and digoxin
51
channels
facilitated diffusion - transport protein assists in movement of a specific S down its concentration gradient ex: aquaporins, stretch-activated ion channels
52
transporters
secondary active transport/ co-transport - transport protein couples movement of a S against it's concentration gradient to the movement of a second S down its concentration gradient
53
GLUT1
uniporter for glucose-facilitated diffusion
54
ABC proteins and disease
ATP-binding cassette proteins - important pumps CFTR -> cystic fibrosis ABCA1 -> Tangier's disease ABCD1 -> ADL ABCG5/8 -> B-sitosterolemia
55
digoxin
- comes from digitalis/foxglove - used for CHF - mechanism: inhibitor of Na/K ATPase - helps heart beat more regularly and strongly
56
NCX
Na+/Ca2+ exchanger - cation antiporter - uses Na gradient to move Ca against its gradient - pumps Ca out of muscle cells