title: Molecular mechanism of P-glycoprotein assembly into cellular membranes.
abstract: In the past decade major advances have been made towards understanding the mechanisms by which polytopic membrane proteins fold and assemble in cellular membranes. In eukaryotes, this process is mediated by a complex set of machinery in the endoplasmic reticulum (ER) that facilitates translocation of peptide loops across and integration of hydrophobic helices into the lipid bilayer. Studies evaluating the biogenesis of P-glycoprotein (P-gp) have been at the forefront of this rapidly expanding field. They have revealed a fascinating although sometimes confusing picture that has challenged our notions about general mechanisms of polytopic protein assembly and questioned specific predictions about the details and uniqueness of P-gp transmembrane topology. This review will attempt to summarize and consolidate our current knowledge of the sequence of events that gives rise to P-gp topology in the ER compartment and the implications of these events for polytopic protein biogenesis and function.
authors.affiliation: Division of Molecular Medicine, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd., Portland, Oregon 97201, USA. skachw@ohsu.edu
authors.forename: Victoria
authors.initials: V
authors.lastname: Anthony
authors.forename: William R
authors.initials: WR
authors.lastname: Skach
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis* / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D017434:Protein Structure, Tertiary
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008051:Lipid Bilayers; D020033:Protein Isoforms