Lipid Protein Ratios
4
Protein Lipid
Axon 75 25
Mitochondrial outer 20 80
Mitochondrial inner 75 25
Plasma 50
50
Membrane Compositions
9
P-Lipid G-Lipid Chol PE PC PG PI PS PA S CL GD SM
Erythrocytes
24 - 9.2 30.2 24.5 - 3 15.1 - - - - 27.2
Myelin 33 22 17 14 11 - - 7 - - - - 6
Microsomes 25 4 7.5
Rod outer 27 9.2 2 30 27.5 - 2 7 - - - - 2
Dynamic Timescales
18
Motion Time Scale -log(s)
Bond vibration -14 to -13
Proton transfer -12
Hydrogen bonding -12 to -11
Rotation of side chains at surface -11 to -10
Helix breakdown/formation -8 to -7
Allosteric transitions -5 to 0
Rotation of sidechains -4 to 0
Lateral Diffusion (1mm) -1 to 0
Lipid Flip Flop (uncatalyzed) 3 to 4
Membrane Proteins
• Membrane proteins account for 25-35% of genome in living organisms.
• There are over >45,000 structures of water-soluble proteins,
• but only ~150 unique structures of membrane proteins.
• Membrane proteins account for ~50% of all therapeutic targets
30
Historical Milestones in Membrane Protein
Structure Determination
• 1977 Bacteriorhodopsin (EM), Henderson and Unwin, Nature
• 1984 Photosynthetic reaction center, Deisenhofer et al, JMB
• 1990 Bacteriorhodopsin, Henderson et al, JMB
• 1992 Porin (beta-barrel), Weiss & Schulz, JMB
• 1998 K+ channel, Doyle et al, Science
• 2000 Rhodopsin, Palczewski et al, Nature
• 2007 GPCR, Rasmussen et al, Nature
34
Gene Duplications • Many helical membrane proteins (~60%) contain homologous domains with
opposite membrane orientation.
• Pseudosymmetry
• Example: Aquaporin 1
44
48
Conformational Energetics of Rhodopsin Modulated by Nonlamellar-Forming Lipids†
Ana Vitória Botelho,‡, Nicholas J. Gibson,§, Robin L. Thurmond,‖,, Yin Wang,#, and, and
Michael F. Brown*,‡,‖ Biochemistry 2002 41 (20), 6354-6368