Extent of structural asymmetry in homodimeric proteins: prevalence and relevance.
Extent of structural asymmetry in homodimeric proteins: prevalence and relevance.
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DOI：
10.1371/journal.pone.0036688
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Srinivasan N
中科院分区：
文献类型：
--
作者：
Swapna LS;Srikeerthana K;Srinivasan N
大多数同源二聚体蛋白质具有对称结构。虽然已知对称性赋予结构和功能优势，但也观察到不对称组织。使用非冗余数据集的223个高分辨率的晶体结构的生物相关的同源二聚体，我们解决的问题的流行和意义的不对称性。我们使用了两种措施来量化全球和接口的不对称性，并评估几个分子和结构参数与不对称性的相关性。我们已经确定了罕见的情况下（11/223），具有明显的全球不对称性的生物学相关的同源二聚体。不对称性作为一种手段，使同二聚体和另一个分子之间的2∶1结合;它也使细胞信号从不对称的大分子配体，如DNA。对这些情况的分析揭示了防止可能的无限阵列形成的两种可能的机制。在同源二聚体通过其三级结构中的非拓扑等价表面缔合的情况下，使用配体依赖性机制。对于通过大表面结合的稳定二聚体，配体依赖性结构变化调节聚合/解聚;对于通过在进化上不很保守的较小表面结合的不稳定二聚体，二聚化仅在配体存在下发生。在同二聚体通过相互作用表面与三级结构中拓扑等价的部分表面缔合的情况下，空间位阻充当无限阵列的预防机制。我们还发现，同源二聚体表现出严重对称的组织很少表现出完美的局部对称性或高局部不对称性。小配体在界面处的结合不会引起界面不对称性的任何显著变化。然而，生物相关的界面不对称性在严重对称的同源二聚体的识别是混淆的存在类似的小幅度的变化所造成的，由于人工结晶。我们的研究提供了新的见解，关于住宿的不对称性同源二聚体。
Most homodimeric proteins have symmetric structure. Although symmetry is known to confer structural and functional advantage, asymmetric organization is also observed. Using a non-redundant dataset of 223 high-resolution crystal structures of biologically relevant homodimers, we address questions on the prevalence and significance of asymmetry. We used two measures to quantify global and interface asymmetry, and assess the correlation of several molecular and structural parameters with asymmetry. We have identified rare cases (11/223) of biologically relevant homodimers with pronounced global asymmetry. Asymmetry serves as a means to bring about 2∶1 binding between the homodimer and another molecule; it also enables cellular signalling arising from asymmetric macromolecular ligands such as DNA. Analysis of these cases reveals two possible mechanisms by which possible infinite array formation is prevented. In case of homodimers associating via non-topologically equivalent surfaces in their tertiary structures, ligand-dependent mechanisms are used. For stable dimers binding via large surfaces, ligand-dependent structural change regulates polymerisation/depolymerisation; for unstable dimers binding via smaller surfaces that are not evolutionarily well conserved, dimerisation occurs only in the presence of the ligand. In case of homodimers associating via interaction surfaces with parts of the surfaces topologically equivalent in the tertiary structures, steric hindrance serves as the preventive mechanism of infinite array. We also find that homodimers exhibiting grossly symmetric organization rarely exhibit either perfect local symmetry or high local asymmetry. Binding of small ligands at the interface does not cause any significant variation in interface asymmetry. However, identification of biologically relevant interface asymmetry in grossly symmetric homodimers is confounded by the presence of similar small magnitude changes caused due to artefacts of crystallisation. Our study provides new insights regarding accommodation of asymmetry in homodimers.
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影响因子：
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通讯作者：
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影响因子：
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