The recently elucidated Get proteins are responsible for the targeted delivery of the majority of tail-anchored (TA) proteins to the endoplasmic reticulum. Get4 and Get5 have been identified in the early steps of the pathway mediating TA substrate delivery to the cytoplasmic targeting factor Get3. Here we report a crystal structure of Get4 and an N-terminal fragment of Get5 from Saccharomyces cerevisae. We show Get4 and Get5 (Get4/5) form an intimate complex that exists as a dimer (two copies of Get4/5) mediated by the C-terminus of Get5. We further demonstrate that Get3 specifically binds to a conserved surface on Get4 in a nucleotide dependent manner. This work provides further evidence for a model in which Get4/5 operates upstream of Get3 and mediates the specific delivery of a TA substrate.
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| http://dx.doi.org/10.1073/pnas.1006036107 | DOI Listing |
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Article Synopsis
- * In Saccharomyces cerevisiae, the GET pathway relies on a sorting complex made up of proteins Sgt2, Get4, and Get5, which help load nascent TA proteins onto the Get3 ATPase, with a protein called Ybr137wp also playing a role in this mechanism.
- * A study detailed the crystal structure of Ybr137wp, revealing it forms a decamer and interacts with Sgt2, suggesting that Ybr137wp
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