Molecular mechanism of P-glycoprotein assembly into cellular membranes.
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.
Anthony
Victoria
V
Division of Molecular Medicine, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Rd., Portland, Oregon 97201, USA. skachw@ohsu.edu
Skach
William R
WR
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
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008051:Lipid Bilayers; D020033:Protein Isoforms