尾锚定蛋白（TA蛋白）在几乎每种细胞膜中调控重要生物化学过程。它们是整体性的膜蛋白，含有一个胞质溶解性N-端区域，该区域被一个跨膜区域锚定在细胞膜上。最近的研究表明，TA蛋白向内质网的定位由胞质溶解性ATP酶伴护蛋白Get3调控。
现在，Get3的晶体结构已以一种“开放的”无核苷酸形式和一种“封闭的”与核苷酸相结合的形式被确定。从开放向封闭的转变导致一个较大的构形变化，露出一个疏水沟，该疏水沟之大足以容纳TA基质。这些结果让我们对TA蛋白由核苷酸调控的结合及释放有了一个机制上的认识。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 461, 361-366 (17 September 2009) | doi:10.1038/nature08319
The structural basis of tail-anchored membrane protein recognition by Get3
Agnieszka Mateja1, Anna Szlachcic1,3, Maureen E. Downing1, Malgorzata Dobosz1,4, Malaiyalam Mariappan2, Ramanujan S. Hegde2 & Robert J. Keenan1
1 Department of Biochemistry & Molecular Biology, The University of Chicago, Gordon Center for Integrative Science, Room W238, 929 East 57th Street, Chicago, Illinois 60637, USA
2 Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Room 101, Building 18T, 18 Library Drive, Bethesda, Maryland 20892, USA
3 Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw, Poland
4 Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30-060 Krakow, Poland
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' (ADPAlF4 --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.
