title: Membrane protein misassembly in disease.
abstract: Helix-helix interactions play a central role in the folding and assembly of integral α-helical membrane proteins and are fundamentally dictated by the amino acid sequence of the TM domain. It is not surprising then that missense mutations that target these residues are often linked to disease. In this review, we focus on the molecular mechanisms through which missense mutations lead to aberrant folding and/or assembly of these proteins, and then discuss pharmacological approaches that may potentially mitigate or reverse the negative effects of these mutations. Improving our understanding of how missense mutations affect the interactions between TM α-helices will increase our capability to develop effective therapeutic approaches to counter the misassembly of these proteins and, ultimately, disease. This article is part of a Special Issue entitled: Protein Folding in Membranes.
authors.affiliation: Division of Molecular Structure & Function, Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Derek P
authors.initials: DP
authors.lastname: Ng
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Poulsen
authors.forename: Charles M
authors.initials: CM
authors.lastname: Deber
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004194:Disease / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense / Q000235:genetics; D017433:Protein Structure, Secondary
chemical_list: D008565:Membrane Proteins