Phenomenological description of the association of protein subunits subjected to conformational drift. Effects of dilution and of hydrostatic pressure

Abstract

The native conformation of oligomers may be expected to undergo reversible changes when they separate upon dissociation of the original aggregate. When these changes are slow in comparison with the time of an association-dissociation (AD) cycle, they give rise to characteristic effects in the dependence of the dissociation: upon dilution, at constant pressure, and upon the applied pressure, at constant concentration. The phenomenological description of these effects is examined by comparing two possible models: The first model assumes a continuous loss in free energy of association with the extent of dissociation; the second supposes the existence of two or more distinct aggregates differing in subunit affinity and present in proportions that vary with the extent of dissociation. The latter model fits better the experimental data available, with regard to both the concentration and the pressure dependence of the association, and gives a particularly simple explanation of the hysteresis phenomena observed in several oligomeric proteins after application of pressure. The validity of the principle of detailed balance, often assumed in dealing with complex equilibria, is discussed in detail as it does not appear possible to reconcile it with some of the experimental observations or with the proposed model.

Pressure treatment of tailspike aggregates rapidly produces on‐pathway folding intermediates

“…After a few hours at atmospheric pressure these aggregates recovered their "atmospheric-pressure" mobilities, indicating that the structural change was reversible. This may be analogous to the conformational drift described by Weber (Weber, 1986;King and Weber, 1986).…”

The preaggregated state of an amyloidogenic protein: Hydrostatic pressure converts native transthyretin into the amyloidogenic state

“…In the 1980s, Gregorio Weber proposed an elegant hypothesis to explain the hysteresis, termed conformational drift. His proposal accounts for the rapid dissociation of an oligomeric protein coupled to a slow isomerization process (a first order-reaction) that takes place after dissociation (47,48). The partial loss of affinity between subunits results from this progressive conformational change upon dissociation.…”

“…The partial loss of affinity between subunits results from this progressive conformational change upon dissociation. Reciprocally, conformational adjustments restoring the original properties of the oligomer occur upon reassociation (47,48).…”

Partially folded states of the capsid protein of cowpea severe mosaic virus in the disassembly pathway

“…However, loss of subunit af®nity after pressure dissociation has been detected for some of these systems (King & Weber, 1986;Silva et al, 1986;Ruan & Weber, 1988). This loss of free energy of association is attributed to conformational changes due to subunit separation; it has been termed conformational drift (Weber, 1986). When Figure 2.…”