J Michael Sauder - Definition of amide protection factors for early kinetic intermediates in protein folding

Version 1

      Publication Details (including relevant citation   information):

      Proc Natl Acad Sci USA (1998) 95: 4299-4302.

      Houry WA, Sauder JM, Roder H, Scheraga HA

      Abstract:

      Hydrogen-deuterium exchange experiments have been used previously   to  investigate the structures of well defined states of a   given protein.  These include the native state, the unfolded   state, and any  intermediates that can be stably populated   at equilibrium. More  recently, the hydrogen-deuterium   exchange technique has been applied in  kinetic labeling   experiments to probe the structures of transiently  formed   intermediates on the kinetic folding pathway of a given   protein.  From these equilibrium and nonequilibrium studies,   protection factors  are usually obtained. These protection   factors are defined as the ratio  of the rate of exchange of   a given backbone amide when it is in a fully    solvent-exposed state (usually obtained from model peptides) to   the rate  of exchange of that amide in some state of the   protein or in some  intermediate on the folding pathway of   the protein. This definition is  straightforward for the   case of equilibrium studies; however, it is less  clear-cut   for the case of transient kinetic intermediates. To clarify    the concept for the case of burst-phase intermediates, we   have  introduced and mathematically defined two different   types of protection  factors: one is P struc, which is more   related to the structure of the  intermediate, and the other   is P app, which is more related to the  stability of the   intermediate. Kinetic hydrogen-deuterium exchange data  from   disulfide-intact ribonuclease A and from cytochrome c are   discussed  to explain the use and implications of these two   definitions.

      Address (URL): http://www.pnas.org/content/95/8/4299.abstract