title: Architecture of the ribosome-channel complex derived from native membranes.
abstract: The mammalian Sec61 complex forms a protein translocation channel whose function depends upon its interaction with the ribosome and with membrane proteins of the endoplasmic reticulum (ER). To study these interactions, we determined structures of "native" ribosome-channel complexes derived from ER membranes. We find that the ribosome is linked to the channel by seven connections, but the junction may still provide a path for domains of nascent membrane proteins to move into the cytoplasm. In addition, the native channel is significantly larger than a channel formed by the Sec61 complex, due to the presence of a second membrane protein. We identified this component as TRAP, the translocon-associated protein complex. TRAP interacts with Sec61 through its transmembrane domain and has a prominent lumenal domain. The presence of TRAP in the native channel indicates that it may play a general role in translocation. Crystal structures of two Sec61 homologues were used to model the channel. This analysis indicates that there are four Sec61 complexes and two TRAP molecules in each native channel. Thus, we suggest that a single Sec61 complex may form a conduit for translocating polypeptides, while three copies of Sec61 play a structural role or recruit accessory factors such as TRAP.
authors.affiliation: Department of Physiology and Biophysics, Boston University School of Medicine, 700 Albany St., Boston, MA 02118-2526, USA.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Ménétret
authors.forename: Ramanujan S
authors.initials: RS
authors.lastname: Hegde
authors.forename: Sven U
authors.initials: SU
authors.lastname: Heinrich
authors.forename: Preethi
authors.initials: P
authors.lastname: Chandramouli
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Ludtke
authors.forename: Tom A
authors.initials: TA
authors.lastname: Rapoport
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Akey
mesh_terms: D000818:Animals; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000737:chemistry* / Q000378:metabolism; D007425:Intracellular Membranes / Q000737:chemistry* / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D012270:Ribosomes / Q000737:chemistry* / Q000378:metabolism*; D000069816:SEC Translocation Channels
chemical_list: D007473:Ion Channels; D008565:Membrane Proteins; D000069816:SEC Translocation Channels