Architecture of the ribosome-channel complex derived from native membranes

被引:110
作者
Ménétret, JF
Hegde, RS
Heinrich, SU
Chandramouli, P
Ludtke, SJ
Rapoport, TA
Akey, CW [1 ]
机构
[1] Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA
[2] NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA
[3] Baylor Coll Med, Nacl Ctr Macromol Imaging, Verna & Marrs Mclean Dept Biochem & Mol Biol, Houston, TX 77030 USA
[4] Harvard Univ, Howard Hughes Med Inst, Sch Med, Boston, MA 02115 USA
[5] Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
ribosome-channel complex; Sec61; TRAP; co-translational translocation;
D O I
10.1016/j.jmb.2005.02.053
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:445 / 457
页数:13
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