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Johnson/Elsevier( m# W6 i. T8 q- E0 U! S4 W D& Z) F/ s
/ L( D0 N2 Z+ v1 i9 e" eNascent transmembrane sequences (TMSs) can, while still well inside the ribosome, fold into an -helix, according to Cheryl Woolhead, Arthur Johnson, and colleagues (Texas A&M, College Station, TX). That -helix appears to send a message through the ribosome to the bound protein translocation apparatus so that it knows when to open and close its various gates.& d" b9 T+ o0 F9 c8 E4 v* ^
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Making a secreted protein is easy: a ribosome docks to the ER translocon, forming a tight seal, and the protein threads through the translocon tunnel. But with transmembrane proteins, the ribosome and translocon must make space for the release of both the TMS into the membrane and any following cytoplasmic loop into the cytoplasm. Previous work suggested that an ion-tight seal is maintained by the binding of BiP to the lumenal surface of the translocon.
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But how does BiP know it is needed? Johnson had earlier established that BiP binding is induced if synthesis is halted just four amino acids after the completion of the TMS, with the TMS still well within the ribosome. "This threw us for a loop," says Johnson. Perhaps the nascent chain tunnel was not a passive tunnel, but a transducer of signals about TMS arrival.
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Johnson now suggests that the ribosome detects a TMS as different based on the TMS's propensity to form an -helix. His evidence for -helix formation consists of fluorescence resonance energy transfer (FRET) between dyes placed at either end of a newly synthesized TMS. Other, presumably extended, sequences showed no such energy transfer.; e+ |* { O. d0 g& P- m
7 ]5 C1 f8 l/ x- qThe TMS makes two unique ribosomal contacts. The first, with L17, coincides with and may induce BiP binding. L17 is a plausible signaler, as it has one end near the site of protein synthesis and the other near the site of contact with the translocon. Further down the tunnel, the TMS contacts L39. This coincides with the later release of the ribosome–translocon seal, which may allow cytoplasmic domains to escape." T+ G% ~* V$ A( Z4 N
2 U- m& k3 ~4 N4 g( ?* ?1 x8 ICrystallographers have suggested a very different model in which the translocon pore forms an adjustable seal. Johnson's model of sequential (ribosome then BiP) seals to the translocon is based on the changing accessibility to fluorescence-quenching ions. Resolution of the issue may have to await the tricky crystallization of a translocon with a bound nascent protein.
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Reference:
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! o9 a, Z! J( c) k$ N1 rWoolhead, C.A., et al. 2004. Cell. 116:725–736.(Helical transmembrane sequences may send) |
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发表于 2009-3-6 08:27
发表于 2015-5-25 19:31
