The Structural Basis of Tail-anchored Membrane Protein Recognition by Get3

Overview

Journal Nature

Specialty Science

Date 2009 Aug 14

PMID 19675567

Citations 106

Authors

Agnieszka Mateja

Anna Szlachcic

Maureen E Downing

Malgorzata Dobosz

Malaiyalam Mariappan

Ramanujan S Hegde

Robert J Keenan

Affiliations

Soon will be listed here.

Abstract

Targeting of newly synthesized membrane proteins to the endoplasmic reticulum is an essential cellular process. Most membrane proteins are recognized and targeted co-translationally by the signal recognition particle. However, nearly 5% of membrane proteins are 'tail-anchored' by a single carboxy-terminal transmembrane domain that cannot access the co-translational pathway. Instead, tail-anchored proteins are targeted post-translationally by a conserved ATPase termed Get3. The mechanistic basis for tail-anchored protein recognition or targeting by Get3 is not known. Here we present crystal structures of yeast Get3 in 'open' (nucleotide-free) and 'closed' (ADP.AlF(4)(-)-bound) dimer states. In the closed state, the dimer interface of Get3 contains an enormous hydrophobic groove implicated by mutational analyses in tail-anchored protein binding. In the open state, Get3 undergoes a striking rearrangement that disrupts the groove and shields its hydrophobic surfaces. These data provide a molecular mechanism for nucleotide-regulated binding and release of tail-anchored proteins during their membrane targeting by Get3.

Citing Articles

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The GET insertase exhibits conformational plasticity and induces membrane thinning.

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