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
Q

ionic detergents

A

SDS (sodium dodeylsulfate)

sodium deoxycholate

26
Q

non-ionic detergents

A

triton X-100

octylglucoside

27
Q

what are lipid rafts?

A

microdomains of specific lipids that cluster together and are different from surrounding lipids

28
Q

components of lipid rafts

A
  • no glycolipids, PE, PC
  • enriched w/ glycosphingolipids and cholesterol
  • enriched for acylated peripheral/integral proteins
29
Q

6 functions of lipid rafts

A
  1. signaling platforms
  2. exocytosis
  3. endocytosis
  4. pathogen entry
  5. apoptosis
  6. cytoskeletal organization
30
Q

functions of membrane fluidity

A
  • response to temp change
  • fusion and fission/sealing damages
  • substrate exchange
  • ETC
  • multiprotein complex formation
31
Q

evidence that proteins and lipids float in plane of membrane comes from….

A
  • cell fusion experiments
  • FRAP
  • patching
  • lazer tweezers
32
Q

FRAP

A

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
Q

do all membrane proteins and lipids diffuse?

A

no

34
Q

when can lipids and proteins be immobilized?

A
  • if in lipid rafts (microdomain)
  • protein-ECM interaction
  • protein-membrane skeleton association
  • cell-cell interaction
35
Q

describe membrane skeleton

A

non-covalent, submembranous array of proteins

36
Q

functions of membrane skeleton

A
  • 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
Q

parts of membrane skeleton

A
  • a and B spectrin
  • ankyrin
  • band 3
  • glycophorin
  • band 4.1
  • actin
38
Q

function of Band 3

A

major integral membrane protein: HCO3-/Cl- antiporter

  • 20-25% of total protein
  • can be cross-linked to ankyrin
39
Q

function of glycophorin

A

integral membrane protein - heavily glycosylated

  • negative charge keeps surface of RBC hydrophilic
  • keeps RBCs from sticking together (charge repulsion)
40
Q

function of band 4.1

A

anchor for spectrin

41
Q

what makes up junctional complex?

A

actin/spectrin binding with band 4.1

42
Q

function of a and B spectrin

A

help RBC change shape

43
Q

spectrin heterodimers

A

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
Q

function of actin in the RBC membrane skeleton

A

present only in small fragments - hub for spectrin molecules to associate to form a filamentous meshwork

45
Q

hereditary spherocytosis mutations

A

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
Q

what molecules are permeable, slightly permeable, impermeable through membrane

A

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
Q

three classes of transport integral membrane proteins

A
  1. channels
  2. transporters
  3. pumps

mediate transport of ions, sugars, aa’s, and other metabolites across cellular membranes

48
Q

pumps

A

active transport - couples movement of S against its concentration gradient to ATP hydrolysis

ex: Na+/K+ pump

49
Q

Na+/K+ pump

A

important plasma membrane protein

-Na out, K in (antiporter)

50
Q

what drugs target Na+/K+ pumps?

A

ouabain and digoxin

51
Q

channels

A

facilitated diffusion - transport protein assists in movement of a specific S down its concentration gradient

ex: aquaporins, stretch-activated ion channels

52
Q

transporters

A

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
Q

GLUT1

A

uniporter for glucose-facilitated diffusion

54
Q

ABC proteins and disease

A

ATP-binding cassette proteins - important pumps

CFTR -> cystic fibrosis
ABCA1 -> Tangier’s disease
ABCD1 -> ADL
ABCG5/8 -> B-sitosterolemia

55
Q

digoxin

A
  • comes from digitalis/foxglove
  • used for CHF
  • mechanism: inhibitor of Na/K ATPase - helps heart beat more regularly and strongly
56
Q

NCX

A

Na+/Ca2+ exchanger

  • cation antiporter
  • uses Na gradient to move Ca against its gradient
  • pumps Ca out of muscle cells