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首页> 外文期刊>Journal of Molecular Biology >Domain Organization of D-AKAP2 Revealed by Enhanced Deuterium Exchange-Mass Spectrometry (DXMS).
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Domain Organization of D-AKAP2 Revealed by Enhanced Deuterium Exchange-Mass Spectrometry (DXMS).

机译：D-AKAP2的域组织由增强的氘交换质谱法（DXMS）揭示。

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摘要

Dual specific A-kinase anchoring protein 2 (D-AKAP2) is a scaffold protein that coordinates cAMP-mediated signaling complexes by binding to type I and type II protein kinase A (PKA). While information is unfolding regarding specific binding motifs, very little is known about the overall structure and dynamics of these scaffold proteins. We have used deuterium exchange-mass spectrometry (DXMS) and limited proteolysis to probe the folded regions of D-AKAP2, providing for the first time insight into the intra-domain dynamics of a scaffold protein. Deuterium on-exchange revealed two regions of low deuterium exchange that were surrounded by regions of high exchange, suggestive of two distinctly folded regions, flanked by disordered or solvent accessible regions. Similar folded regions were detected by limited proteolysis. The first folded region contained a putative regulator of G-protein signaling (RGS) domain. A structural model of the RGS domain revealed that the more deuterated regions mapped onto loops and turns, whereas less deuterated regions mapped onto alpha-helices, consistent with this region folding into an RGS domain. The second folded region contained a highly protected PKA binding site and a more solvent-accessible PDZ binding motif, which may serve as a potential targeting domain for D-AKAP2. DXMS has verified the multi-domain architecture of D-AKAP2 implied by sequence homology and has provided unique insight into the accessibility of the PKA binding site.
机译：双重特异性A激酶锚定蛋白2（D-AKAP2）是一种支架蛋白，通过与I型和II型蛋白激酶A（PKA）结合来协调cAMP介导的信号复合物。尽管有关特定结合基序的信息正在展开，但对这些支架蛋白的整体结构和动力学知之甚少。我们已经使用氘交换质谱（DXMS）和有限的蛋白水解来探测D-AKAP2的折叠区域，首次提供了支架蛋白的域内动态的见解。氘交换显示氘交换低的两个区域被交换高的区域包围，暗示两个明显折叠的区域，两侧为无序或溶剂可及区域。通过有限的蛋白水解检测到相似的折叠区域。第一个折叠区域包含一个假定的G蛋白信号（RGS）结构调节子。 RGS结构域的结构模型显示，更多氘代区域映射到环和匝，而更少氘代区域映射到α-螺旋，与此区域折叠成RGS域一致。第二折叠区域包含高度保护的PKA结合位点和更易接近溶剂的PDZ结合基序，其可以用作D-AKAP2的潜在靶向域。 DXMS已验证了序列同源性暗示的D-AKAP2的多域结构，并提供了对PKA结合位点可及性的独特见解。

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