Translocation channel gating kinetics balances protein translocation efficiency with signal sequence recognition fidelity.

Abstract:

:The transition between the closed and open conformations of the Sec61 complex permits nascent protein insertion into the translocation channel. A critical event in this structural transition is the opening of the lateral translocon gate that is formed by four transmembrane (TM) spans (TM2, TM3, TM7, and TM8 in Sec61p) to expose the signal sequence-binding site. To gain mechanistic insight into lateral gate opening, mutations were introduced into a lumenal loop (L7) that connects TM7 and TM8. The sec61 L7 mutants were found to have defects in both the posttranslational and cotranslational translocation pathways due to a kinetic delay in channel gating. The translocation defect caused by L7 mutations could be suppressed by the prl class of sec61 alleles, which reduce the fidelity of signal sequence recognition. The prl mutants are proposed to act by destabilizing the closed conformation of the translocation channel. Our results indicate that the equilibrium between the open and closed conformations of the protein translocation channel maintains a balance between translocation activity and signal sequence recognition fidelity.

journal_name

Mol Biol Cell

authors

Trueman SF,Mandon EC,Gilmore R

doi

10.1091/mbc.E11-01-0070

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

2983-93

issue

17

eissn

1059-1524

issn

1939-4586

pii

mbc.E11-01-0070

journal_volume

22

pub_type

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