尾錨定蛋白（TA蛋白）在幾乎每種細胞膜中調(diào)控重要生物化學(xué)過程,。它們是整體性的膜蛋白，含有一個胞質(zhì)溶解性N-端區(qū)域,，該區(qū)域被一個跨膜區(qū)域錨定在細胞膜上,。最近的研究表明，TA蛋白向內(nèi)質(zhì)網(wǎng)的定位由胞質(zhì)溶解性ATP酶伴護蛋白Get3調(diào)控,。
現(xiàn)在,，Get3的晶體結(jié)構(gòu)已以一種“開放的”無核苷酸形式和一種“封閉的”與核苷酸相結(jié)合的形式被確定。從開放向封閉的轉(zhuǎn)變導(dǎo)致一個較大的構(gòu)形變化,，露出一個疏水溝,，該疏水溝之大足以容納TA基質(zhì)。這些結(jié)果讓我們對TA蛋白由核苷酸調(diào)控的結(jié)合及釋放有了一個機制上的認識,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
