Sec61 forms the pore through which proteins enter the ER. On page 67, Cheng et al. show that its cytoplasmic face makes at least two contributions to translocation before the protein passage event.The predicted structure of yeast Sec61 suggests that several conserved charged residues, which are in cytoplasmic loops that link adjacent membrane-spanning domains, may interact with the ribosome during cotranslational translocation. The authors mutated many of these candidate residues within Sec61. Several of the mutations blocked cotranslational protein translocation in vivo, but the particular effect depended on which loop was mutated., ^" S6 H' ~2 g0 b. Y: d1 e6 y
- s% D: t: T% \8 y+ ? _& B& D G
Point mutations in loop 8 (L8) interfered with the binding affinity between the ribosomal large subunit and the pore. Without this contact, normally ER-localized proteins accumulated in the cytoplasm. Cytoplasmic protein accumulation was also seen when loop 6 (L6) was mutated, although the binding affinity of the L6 mutants for the ribosome was not affected, suggesting that the cytoplasmic face of Sec61 has yet another function in translocation. & Q" v8 D* Q6 ~* ?6 x" I& E: r% s9 {8 f0 @8 M0 e C; C
This function might be to improve the efficiency of ribosome binding by signaling that a channel is unoccupied. Before transfering to the translocon, the ribosome first binds to the signal recognition particle (SRP) and its receptor (SR). The authors hypothesize that interactions between an unoccupied L6 and the SR might place the SR-SRP-ribosome intermediate near open channels and thus hasten its transfer. They are now looking for definitive evidence of L6–receptor interactions.# G5 \& S0 n+ a! E4 ]8 E5 ^7 }7 g, H# z$ F
7 x- q5 g$ P2 s5 b cNicole LeBrasseur4 `6 j# I; h: N$ N
' Z, {2 g! D6 _: ] e6 H0 E
lebrasn@rockefeller.edu 3 q8 k" N$ g, R! S, x+ {5 k; [ 5 D' b. w3 C. `0 d* o& U1 c; CZhiliang Cheng, Ying Jiang, Elisabet C. Mandon, and Reid Gilmore * d6 v# s2 v. T+ j2 N) E4 K3 f$ C# n$ I+ V1 O9 L+ p+ H
J. Cell Biol. 2005 168: 67-77.(Mutations in L6 (blue) and L8 (white) de)作者: tuanzi 时间: 2015-5-25 13:18