Protonation of model ionizable sidechains in transmembrane protein domains

Abstract

The ionization states of individual amino acid residues of membrane proteins in lipid membrane environment are difficult to decipher or assign directly. The effective pK(a) values of protein groups are determined by a complex interplay between local polarity, Coulomb interactions, and structural reorganizations. The analysis is further complicated by the dearth of information about gradients in polarity, electric potentials, and hydration at the protein-membrane interface. In this work we report on a spin-labeling EPR method for assessing effects of membrane surface potential, local environment at the protein-membrane interface, and water penetration along this interface on effective pK(a) of membrane-buried ionizable groups.