Download MendeleyThe Structural Basis of Tail-Anchored Membrane Protein Recognition by Get3.
Mateja, A., Szlachcic, A., Downing, M.E., Dobosz, M., Mariappan, M., Hegde, R.S., Keenan, R.J.(2009) Nature 461: 361
- PubMed: 19675567
- DOI: https://doi.org/10.1038/nature08319
- Primary Citation of Related Structures:
2WOJ, 2WOO - PubMed 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.
Organizational Affiliation:
Department of Biochemistry & Molecular Biology, The University of Chicago, Gordon Center for Integrative Science, Room W238, 929 East 57th Street, Chicago, Illinois 60637, USA.
