Dipole-Potential-Mediated Effects on Ion Pump Kinetics.

Abstract:

:The kinetics of conformational changes of P-type ATPases necessary for the occlusion or deocclusion of transported ions are known to be sensitive to the composition of the surrounding membrane, e.g., phospholipid content, mole percentage of cholesterol, and the presence of lipid-bound anions. Research has shown that many membrane components modify the dipole potential of the lipid head-group region. Based on the observation that occlusion/deocclusion reactions of ion pumps perturb the membrane surrounding the protein, a mechanism is suggested whereby dipole potential modifiers induce preferential stabilization or destabilization of occluded or nonoccluded states of the protein, leading to changes in the forward and backward rate constants for the transition. The mechanism relies on the assumption that conformational changes of the protein are associated with changes in its hydrophobic thickness that requires a change in local lipid packing density to allow hydrophobic matching with the membrane. The changes in lipid packing density cause changes in local lipid dipole potential that are responsible for the dependence of conformational kinetics on dipole potential modifiers. The proposed mechanism has the potential to explain effects of lipid composition on the kinetics of any membrane protein undergoing significant changes in its membrane cross-sectional area during its activity.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Clarke RJ

doi

10.1016/j.bpj.2015.08.022

subject

Has Abstract

pub_date

2015-10-20 00:00:00

pages

1513-20

issue

8

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(15)00857-7

journal_volume

109

pub_type

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