title: Positive cooperativity without domains or subunits in a monomeric membrane channel.
abstract: The monomeric VDAC channel shows an accelerated pH titration of its transport properties with a Hill coefficient of about 2. This manifests itself as a sharp peak in conductance noise as well as a fast change in channel selectivity with pH. On the basis of the known structure of this channel, we propose that this cooperativity arises from a mechanically linked mobile pair of ionizable groups. Concerted movement of these groups between two states changes the distance from nearby electrostatic charge to influence the pK of the groups. This model of pH-dependent motion produces positive cooperative behavior that fits the observations without need for subunits or identifiable domains within the protein. The mathematical formalism has never required such domains, but these are generally considered an essential part of cooperative behavior in proteins. The present proposal reduces the size of a cooperative unit to a minimum, extending the limits of what is perceived to be possible. Together with large-scale conformational transitions, these subtle cooperative structural changes may allow proteins to adapt, with high sensitivity, to changes in their environment. They might also be relatively easy to engineer into a protein.
authors.affiliation: Laboratory of Physical and Structural Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-0924, USA.
authors.forename: T K
authors.initials: TK
authors.lastname: Rostovtseva
authors.forename: T T
authors.initials: TT
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Colombini
authors.forename: V A
authors.initials: VA
authors.lastname: Parsegian
authors.forename: S M
authors.initials: SM
authors.lastname: Bezrukov
mesh_terms: D000494:Allosteric Regulation; D001692:Biological Transport; D004553:Electric Conductivity; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000378:metabolism*; D008928:Mitochondria; D008962:Models, Theoretical; D009492:Neurospora crassa; D018272:Porins / Q000378:metabolism*; D017186:Titrimetry; D050994:Voltage-Dependent Anion Channels
chemical_list: D007473:Ion Channels; D018272:Porins; D050994:Voltage-Dependent Anion Channels