Secondary Structure of the Novel Myosin Binding Domain WYR and Implications within Myosin Structure.
Secondary Structure of the Novel Myosin Binding Domain WYR and Implications within Myosin Structure.
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DOI：
10.3390/biology10070603
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发表时间：
2021-06-29
期刊：
影响因子：
4.2
通讯作者：
Vigoreaux JO
中科院分区：
文献类型：
--
作者：
Menard LM;Wood NB;Vigoreaux JO
WYR是肌肉蛋白飞行蛋白的一个保守结构域，估计起源于六足动物和甲壳类动物的祖先~500 MYA。本研究表征了WYR的二级结构，并表明它结合了肌球蛋白的卷曲-线圈基序并改变了其结构特性。表征WYR及其与肌凝蛋白的作用为了解推动昆虫成功的持久进化过程提供了有价值的见解。WYR和肌球蛋白之间的关系进一步揭示了一种超微结构调控手段，能够为肌肉的机械性能和结构稳定性所必需的分子结构-功能关系提供信息。肌凝蛋白II轻肌凝蛋白（LMM）的结构变化影响粗丝力学性能和肌肉功能，由LMM结合蛋白调节。飞行蛋白是果蝇间接飞行肌（IFM）功能不可缺少的lmm结合蛋白。Flightin具有三结构域结构，其中包括WYR，这是一个在整个pancrustaceae中保守的新颖的52 aa结构域。在本研究中，我们(i)检验了WYR与LMM结合的假设，（ii）表征了WYR的二级结构，（iii）检验了WYR对LMM的结构影响。260 ~ 190 nm的圆二色性揭示了WYR的结构轮廓，并支持WYR和LMM之间的相互作用。WYR-LMM相互作用由共沉降支持，化学计量比为~2.4:1。WYR-LMM相互作用导致整体线圈含量增加，同时减少螺旋含量。WYR由15%的匝数、31%的反平行β和48%的“其他”成分组成。我们提出了一种WYR结构模型，由Q92-K114之间以ASX为中心的反平行β发夹或围绕N102的β转弯组成，在G117处有G1凸起。使用的果蝇LMM片段V1346-I1941包含保守的跳跃残基2-4，被发现具有传统的螺旋轮廓，但通过多种反褶积方法解释为螺旋含量<30%。这种低螺旋度可能与溶液中结构的动力学行为有关，也可能与c端包含已知的非螺旋区域有关。我们的研究结果支持了WYR与LMM结合的假设，这种相互作用带来了卷曲线圈的结构变化。这些研究表明，通过WYR结构域，飞行蛋白与LMM二级结构的明显变化有关，这种变化可能影响粗丝的结构特性和稳定性，进而影响整个肌肉功能的调节。
WYR is a conserved protein domain characteristic of the muscle protein flightin, estimated to have originated in the ancestor to hexapods and crustaceans ~500 MYA. This study characterizes the secondary structure of WYR and shows that it binds the coiled-coil motif of muscle myosin and changes its structural properties. Characterizing WYR and its role in conjunction with myosin provides valuable insight into enduring evolutionary processes driving the success of Insecta. The relationship between WYR and myosin further reveals a means of ultrastructural regulation capable of informing the molecular structure–function relationships essential for the mechanical properties and structural stability of muscle. Structural changes in the myosin II light meromyosin (LMM) that influence thick filament mechanical properties and muscle function are modulated by LMM-binding proteins. Flightin is an LMM-binding protein indispensable for the function of Drosophila indirect flight muscle (IFM). Flightin has a three-domain structure that includes WYR, a novel 52 aa domain conserved throughout Pancrustacea. In this study, we (i) test the hypothesis that WYR binds the LMM, (ii) characterize the secondary structure of WYR, and (iii) examine the structural impact WYR has on the LMM. Circular dichroism at 260–190 nm reveals a structural profile for WYR and supports an interaction between WYR and LMM. A WYR–LMM interaction is supported by co-sedimentation with a stoichiometry of ~2.4:1. The WYR–LMM interaction results in an overall increased coiled-coil content, while curtailing ɑ helical content. WYR is found to be composed of 15% turns, 31% antiparallel β, and 48% ‘other’ content. We propose a structural model of WYR consisting of an antiparallel β hairpin between Q92-K114 centered on an ASX or β turn around N102, with a G1 bulge at G117. The Drosophila LMM segment used, V1346-I1941, encompassing conserved skip residues 2-4, is found to possess a traditional helical profile but is interpreted as having <30% helical content by multiple methods of deconvolution. This low helicity may be affiliated with the dynamic behavior of the structure in solution or the inclusion of a known non-helical region in the C-terminus. Our results support the hypothesis that WYR binds the LMM and that this interaction brings about structural changes in the coiled-coil. These studies implicate flightin, via the WYR domain, for distinct shifts in LMM secondary structure that could influence the structural properties and stabilization of the thick filament, scaling to modulation of whole muscle function.
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影响因子：
14.9
作者：
Buchan, Daniel W. A.;Jones, David T.
通讯作者：
Jones, David T.
DOI：
10.1073/pnas.0900107106
发表时间：
2009-04-14
影响因子：
11.1
作者：
Armel, Thomas Z.;Leinwand, Leslie A.
通讯作者：
Leinwand, Leslie A.
影响因子：
13.8
作者：
Combet, C;Blanchet, C;Deléage, G
通讯作者：
Deléage, G
影响因子：
5.8
作者：
Cuff, JA;Clamp, ME;Barton, GJ
通讯作者：
Barton, GJ
影响因子：
6.8
作者：
Blanco, F;Ramírez-Alvarado, M;Serrano, L
通讯作者：
Serrano, L