title: Peptide models of membrane protein folding.
abstract: Given the central roles of membrane proteins in cellular processes ranging from nutrient uptake to cell-cell communication, as well as the importance of these proteins as drug targets, efforts to understand and control their structures are vital in human health and disease. The rational design of membrane proteins with modified properties is thus a highly desirable goal in molecular medicine and biotechnology. However, experimental data showing how individual transmembrane (TM) residues and/or segments direct the packing and folding of membrane proteins into biologically functional entities remain sparse. To address these questions in a systematic manner, helix-helix interactions between two (or more) TM segments must be identified and analyzed. Here we present an overview of the utilization of peptides as models of the TM segments of alpha-helical membrane proteins in uncovering the amino acid sequence motifs and interactions that build these molecules. TM peptide design and production strategies are discussed, and specific examples of the application of TM peptides to the study of membrane proteins are presented. We demonstrate that TM peptides can be routinely produced in sufficient quantities for biophysical analysis, are amenable to a variety of experimental techniques, and can effectively replicate the native helix-helix contacts and key aspects of the natural biological structures of membrane proteins.
authors.affiliation: Division of Molecular Structure and Function, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8.
authors.forename: Arianna
authors.initials: A
authors.lastname: Rath
authors.forename: David V
authors.initials: DV
authors.lastname: Tulumello
authors.forename: Charles M
authors.initials: CM
authors.lastname: Deber
mesh_terms: D008565:Membrane Proteins / Q000737:chemistry*; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis*; D017510:Protein Folding
chemical_list: D008565:Membrane Proteins; D010455:Peptides