Water: Foldase activity in catalyzing polypeptide conformational rearrangements

Abstract

Polypeptide conformer interconversion in a low dielectric environment is shown to be highly dependent on water concentration. Water increases this rate by 10 3 , apparently by catalyzing hydrogen bond exchange, and thereby presenting functional properties analogous to that of a foldase. This catalytic effect is demonstrated on the interconversion of a parallel gramicidin dimer into an antiparallel dimer. A Hill coefficient of 6.5 is observed, illustrating the highly cooperative nature of the process. Protein folding in nonpolar environs, such as the hydrophobic core of a protein or the hydrophobic domain of a lipid bilayer, may be contingent on and rate-limited by the scarcity of water.

Lipid bilayers: an essential environment for the understanding of membrane proteins

“…50 In addition, water which, if present, would act as a catalyst for hydrogen bond rearrangements 22 by destabilizing hydrogen bonds and stabilizing the N-H and C O intermediates in such a rearrangement, but this is very scarce in membrane interstices. Therefore, once formed, helices are not likely to rearrange hydrogen-bonding patterns.…”

Reproducible Polypeptide Folding and Structure Prediction using Molecular Dynamics Simulations

“…In particular, it has been shown that water can "lubricate" conformational transitions in proteins and peptides, 35 and catalyze protein folding. 36 Here, we investigate the folding of chignolin in both water and in vacuo using REMD simulations, starting always from extended configurations. The REMD technique 22 allows for significantly enhanced sampling of conformations, due to frequent switching of simulation temperatures (based on a Metropolis criterion) between a number of concurrent simulations.…”

Backbone structure of a small helical integral membrane protein: A unique structural characterization

“…Although the hydrophobic membrane interstices provide an environment that stabilizes uniform a-helices the very high dielectric constant (>200) 67 of the bilayer interface may have the opposite influence. This is not to say that the micelle interface does not aid in the formation of helices, 63,65 but increased competition for hydrogen bonds promotes hydrogen bond exchange 68,69 and potentially allows for a variety of helical structures (J.R. Long, personal communication). Consequently, the uniformity of helical structures may be reduced in this interfacial environment, whether it be in a micelle or bilayer.…”