Download Is the decision based on simple thermodynamics?

Is the decision based on simple thermodynamics?
Bowie NATURE
Vol 433, 27,Jan 2005, Seite 367-369
Experimental approach: Integration of designend TM segments into the
microsomal membrane
degree of membrane integration of the H-segment from SDS–
PAGE gels by measuring the fraction of singly (f 1g) versus singly
plus doubly (f 2g) glycosylated Lep molecules:
p = f1g/(f1g + f2g)
The apparent equilibrium constant between the membrane
integrated and non-integrated forms :
Kapp = f1g/f2g
Gapp = -RTlnKapp
Apparent free energy (DGapp=‐RT lnKapp) values for test segments with 2‐4 Leu residues
Biological hydrophobicity scale
Hessa et al., Nature (2005) 433:377‐81
Correlation between the biological and the Wimley–White water/octanol free
energy scale
Hessa et al., Nature (2005) 433:377‐81
Hydration of small and large hydrophobic solutes
The most important physical feature responsible for hydrophobic
effects: acting like cavities in the water, the hydrophobic solutes
exclude water molecules from the volumes they occupy, and they
present regions of space where hydrogen bonding cannot occur
Chandler, Nature (2005) 437:640-647
MD-simulations:
Snapshot of the solute–water
interface for a purely repulsive
solute with s 4.5 nm at ambient
conditions. Water molecules are
shown in red (oxygen) and white
(hydrogen). The dashed green
circle indicates the apparent solute
size R.
Mittal & Hummer, PNAS (2008) 105:20130-5
Apolar surface area determines the efficiency of translocon‐mediated membrane‐
protein integration into the endoplasmic reticulum
Ojemalm et al Proc.Natl.Acad.Sci.U.S.A 108 (31):E359‐E364, 2011.
An amino acid’s contribution
to the apparent free energy of membrane‐
insertion is directly proportional to the nonpolar accessible surface area of its side chain, as expected for thermodynamic partitioning between aqueous
and nonpolar phases. Unlike bulk‐phase partitioning, characterized by a nonpolar solvation parameter of 23 cal∕mol ∙ Å2, the
solvation parameter for transfer from translocon to bilayer is
6–10 cal∕mol ∙ Å2, pointing to important differences between
translocon‐guided partitioning and simple water‐to‐membrane
partitioning
Ojemalm et al Proc.Natl.Acad.Sci.U.S.A 108 (31):E359‐E364, 2011.
Ojemalm et al Proc.Natl.Acad.Sci.U.S.A 108 (31):E359‐E364, 2011.
Apparent free energy of insertion
Ojemalm et al Proc.Natl.Acad.Sci.U.S.A 108 (31):E359-E364, 2011.
Apolar surface area determines the efficiency of translocon-mediated
membrane-protein integration into the endoplasmic reticulum
Ojemalm et al Proc.Natl.Acad.Sci.U.S.A 108 (31):E359-E364, 2011.