Kinetic stability of membrane proteins
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REVIEW
Kinetic stability of membrane proteins F. Luis González Flecha 1
Received: 15 June 2017 / Accepted: 29 August 2017 # International Union for Pure and Applied Biophysics (IUPAB) and Springer-Verlag GmbH Germany 2017
Abstract Although membrane proteins constitute an important class of biomolecules involved in key cellular processes, study of the thermodynamic and kinetic stability of their structures is far behind that of soluble proteins. It is known that many membrane proteins become unstable when removed by detergent extraction from the lipid environment. In addition, most of them undergo irreversible denaturation, even under mild experimental conditions. This process was found to be associated with partial unfolding of the polypeptide chain exposing hydrophobic regions to water, and it was proposed that the formation of kinetically trapped conformations could be involved. In this review, we will describe some of the efforts toward understanding the irreversible inactivation of membrane proteins. Furthermore, its modulation by phospholipids, ligands, and temperature will be herein discussed. Keywords Thermal stability . Irreversible denaturation . Kinetic analysis . Membrane enzymes . P-ATPases . Protein unfolding
Introduction Soluble and membrane proteins are the two main structural classes of proteins. Membrane proteins constitute a heterogeneous group of proteins, including transporters, receptors, and This article is part of a Special Issue on ‘Latin America’ edited by Pietro Ciancaglini and Rosangela Itri. * F. Luis González Flecha [email protected] 1
Universidad de Buenos Aires, CONICET, Laboratorio de Biofísica Molecular, Instituto de Química y Fisicoquímica Biológicas, Buenos Aires, Argentina
channels, sharing the characteristic of being embedded into biological membranes. They represent about 25–30% of total proteins codified in known genomes (Almén et al. 2009; Wallin and Von Heijne 1998) and constitute the target of about 70% of current drugs (Yildirim et al. 2007). Whereas globular proteins are folded around a hydrophobic core surrounded by a water-accessible surface (Creighton 1996), membrane proteins have some of their more hydrophobic residues interacting with phospholipids, thus defining a hydrophobic transmembrane surface in the protein, and a monolayer of lipids with restricted mobility covering it (Marsh 2008). Multidomain membrane proteins constitute a very interesting subgroup of membrane proteins which are involved in essential cellular functions, such as active transport and signal transduction. They contain a membrane-associated region and one or more waterrelated domains. The synchronized interaction among these regions determines the coupling between cytoplasmic-related biological activities (e.g., molecular recognition, catalysis, etc.) and protein interactions with membrane lipids, which determine membrane-associated biological processes (e.g., transport). As some of these proteins are involved in the movement of hydrophilic species across membranes, the core of the transm
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