Membrane Proteins

1
Membrane Proteins

• Concepts to learn today
• The interplay between the bilayer hydrophobic
  interfacial environment and the protein which
  dictate the membrane protein fold
• How membrane proteins provide a solution to the
  question of how charged and polar molecules
  traverse bilayers

2
General Information

• Plasma membrane 40 angstroms
• thick
• Consists mainly of lipids and proteins.
• Addition of makes membrane
  more rigid.
• When fragmented, will form vesicles.
• Acts as a permeability barrier.
• Selective Permeability provided by

Cholesterol
3
Membrane Proteins

• Transmembrane Proteins pass through membrane
  multiple times as a-helices or ß strands.
• Other Membrane Proteins do not transverse
  membrane, but are attached on one side of the
  membrane by an a-helix or fatty acid.

Figure 12.1
4
Detergents

• The outer surface of membrane proteins have
  hydrophilic and hydrophobic areas.
• Cant be solubilized in aqueous or organic
  solvents.

Figure 12.2 b
5
Bacteriorhodopsin
Fig 12.5

• 7 transmembrane a-helices
• Binds Retinaldehyde via a Schiff Base, a covalent
  bond between K216 and retinal.
• Molecular switch which transforms light energy
  into a H electrochemical gradient, i.e., a H
  pump
• It catalyzes vectorial H transport by a H
  -relay mechanism A H from the Schiff base is
  donated to Asp85 while a H from Asp 96
  reprotonates the Schiff base

6
Bacteriorhodopsin
7
Bacteriorhodopsin
8

• Bacteriorhodopsin exists in 2 states
• Tense (T) binds trans-retinal
• Relaxed (R) binds cis-retinal
• T state Schiff Base is protonated ? Excitation
  by photon ? Isomerization ? H transferred from
  Schiff base to Asp 85
• R state H transferred from Asp 96 to Schiff
  base and H from Asp 85 is transferred to
  Extracellular Space ? H transferred from
  Cytoplasm to Asp 96

9
Photosiomerization of retinal
10
Bacteriorhodopsin photocycle
11
Bacteriorhodopsin photocycle
12
Bacteriorhodopsin photocycle
13
Porin
Fig12.7

• Homotrimeric protein.
• Each monomer is made of a 16 stranded Up/Down ß
  Barrel.
• Subunits interact by polar loop and hydrophobic
  side chain interactions.
• Periplasmic End short and smooth
• Cytoplasmic End funnel shaped, made of long
  loops with hydrophilic residues.
• Eyelet loop connecting ß5 and ß6 extending into
  the central open cavity of the barrel.
• Cavity is lined with charged residues, arranged
  in an electrochemical gradient.

14
Porin Aromatic Belt

• Aromatic Belt mainly Phe and Tyr
• Has polar and hydrophobic character to
  interactive with the hydrophilic space of the
  membrane extracellular solution and hydrophobic
  internal space of the membrane.
• Helps stabilize protein in membrane.

15
K Ion Channel
Fig 12.9

• Homotetrameric protein.
• Ion pore made between the four monomers.
• Each monomer is made of 2 transmembrane
  a-helices, 1 pore helix and a cytosolic tail.
• Selectivity Filter formed from the backbone
  carbonyl Oxygens from the loops connecting pore
  helix to the inner transmembrane helix.
• The structure is stabilized by the packing
  of residues from the loop into the pore helix.

Figure 12.10
16
How is the channel only selective for K ions?

• K (OH2)8 hydration shell (8 H2O needed to
  stabilize K ion)
• Within the K Ion Channel only
• Resolvation Energy Desolvation Energy
• Na (OH2)6 hydration shell (6 H2O needed to
  stabilize Na ion)
• Within the K Ion Channel only
• Resolvation Energy ltltlt Desolvation Energy
• As a K ion enters the selectivity filter,
• repulsive force from the next K ion
• entering the filter will push the first ion
• through the protein out of the cell.

Fig 12.11