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Comparative analyses of the thermodynamic RNA binding signatures of different types of RNA recognition motifs

机译:不同类型的RNA识别基序的热力学RNA结合特征的对比分析

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摘要

RNA recognition motifs (RRMs) are structurally versatile domains important in regulation of alternative splicing. Structural mechanisms of sequence-specific recognition of single-stranded RNAs (ssRNAs) by RRMs are well understood. The thermodynamic strategies are however unclear. Therefore, we utilized microcalorimetry and semi-empirical analyses to comparatively analyze the cognate ssRNA binding thermodynamics of four different RRM domains, each with a different RNA binding mode. The different binding modes are: canonical binding to the beta-sheet surface; canonical binding with involvement of N- and C-termini; binding to conserved loops; and binding to an alpha-helix. Our results identify enthalpy as the sole and general force driving association at physiological temperatures. Also, networks of weak interactions are a general feature regulating stability of the different RRM-ssRNA complexes. In agreement, non-polyelectrolyte effects contributed between similar to 75 and 90% of the overall free energy of binding in the considered complexes. The various RNA binding modes also displayed enormous heat capacity differences, that upon dissection revealed large differential changes in hydration, conformations and dynamics upon binding RNA. Altogether, different modes employed by RRMs to bind cognate ssRNAs utilize various thermodynamics strategies during the association process.
机译:RNA识别基序(RRMS)是在结构上的通用结构域,其在替代剪接的调节中重要。 RRMS通过RRMS对单链RNA(SSRNA)的序列特异性识别的结构机制。然而,热力学策略不清楚。因此,我们利用微量微量微量测定法和半经验分析来相互分析四种不同RRM结构域的同源SSRNA结合热力学,各自具有不同的RNA结合模式。不同的粘合模式是:与β-片表面的典型结合;典型结合与N-和C-Termini的参与;与保守环绑定;并与alpha-helix结合。我们的结果鉴定了生理温度的唯一和一般部队驾驶结合的焓。此外,弱相互作用网络是不同RRM-SSRNA复合物的一般特征调节稳定性。在一致中,非聚电解质效应在所考虑的复合物中相似至75%和90%的结合的总体自由能。各种RNA结合模式也表现出巨大的热容差,即在解剖时显示出在结合RNA时水合,构象和动力学的大差异变化。完全,RRMS采用的不同模式结合同源SSRNA在结合过程中利用各种热力学策略。

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