Mechanism of Assembly of a Substrate Transfer Complex during Tail-anchored Protein Targeting
作者： Harry B. Gristick , Michael E. Rome , Justin W. Chartron , Meera Rao , Sonja Hess
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摘要: Tail-anchored (TA) proteins, defined as having a single transmembrane helix at their C terminus, are post-translationally targeted to the endoplasmic reticulum membrane by guided entry of TA proteins (GET) pathway. In yeast, handover substrates is mediated heterotetrameric Get4/Get5 complex (Get4/5), which tethers co-chaperone Sgt2 targeting factor, Get3 ATPase. Binding Get4/5 critical for efficient targeting; however, questions remain about formation Get3·Get4/5 complex. Here we report crystal structures from Saccharomyces cerevisiae 2.8 and 6.0 A that reveal novel interface between Get4 dominated electrostatic interactions. Kinetic mutational analyses strongly suggest these represent an on-pathway intermediate rapidly assembles then rearranges final Furthermore, provide evidence heterotetramer bound one monomer dimer, uncovering intriguing asymmetry in upon binding. Ultrafast diffusion-limited electrostatically driven association enables sample capture different stages GET
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