Comparative Structural Analysis of Human DEAD-Box RNA Helicases
Comparative Structural Analysis of Human DEAD-Box RNA Helicases
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DOI：
10.1371/journal.pone.0012791
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发表时间：
2010-09-30
期刊：
影响因子：
3.7
通讯作者：
Schuler, Herwig
中科院分区：
文献类型：
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作者：
Schutz, Patrick;Karlberg, Tobias;Schuler, Herwig
死亡盒RNA解旋酶在RNA参与的所有过程中发挥着各种各样的作用，通常是关键的作用。这个蛋白质家族的成员与人类疾病有关，包括癌症和病毒感染。DEAD盒蛋白含有两个保守的结构域，这两个结构域都有助于RNA和ATP结合。尽管最近的进展，这些酶如何将化学能转化为RNA重塑的分子细节是未知的。我们提出了人DDX 2A/eIF 4A 1、DDX 2B/eIF 4A 2、DDX 5、DDX 10/DBP 4、DDX 18/myc调节的DEAD盒蛋白、DDX 20、DDX 47、DDX 52/ROK 1和DDX 53/CAGE的分离的DEAD结构域，以及DDX 25和DDX 41的解旋酶结构域的晶体结构。与先前的知识，这使得一个家庭范围内的比较结构分析。我们提出了一个通用的机制，开放的RNA结合位点。该分析还提供了对DExD/H-蛋白多样性的见解，对理解单个家族成员的功能具有意义。
DEAD-box RNA helicases play various, often critical, roles in all processes where RNAs are involved. Members of this family of proteins are linked to human disease, including cancer and viral infections. DEAD-box proteins contain two conserved domains that both contribute to RNA and ATP binding. Despite recent advances the molecular details of how these enzymes convert chemical energy into RNA remodeling is unknown. We present crystal structures of the isolated DEAD-domains of human DDX2A/eIF4A1, DDX2B/eIF4A2, DDX5, DDX10/DBP4, DDX18/myc-regulated DEAD-box protein, DDX20, DDX47, DDX52/ROK1, and DDX53/CAGE, and of the helicase domains of DDX25 and DDX41. Together with prior knowledge this enables a family-wide comparative structural analysis. We propose a general mechanism for opening of the RNA binding site. This analysis also provides insights into the diversity of DExD/H- proteins, with implications for understanding the functions of individual family members.