Human Tonic and Phasic Smooth Muscle Myosin Isoforms Are Unresponsive to the Loop 1 Insert.
Human Tonic and Phasic Smooth Muscle Myosin Isoforms Are Unresponsive to the Loop 1 Insert.
复制标题
人类强直肌和阶段性平滑肌肌球蛋白亚型对 Loop 1 插入物没有反应。
DOI：
10.1155/2013/634341
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Burghardt,ThomasP
中科院分区：
文献类型：
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作者：
Ajtai,Katalin;Mayanglambam,Azad;Wang,Yihua;Burghardt,ThomasP
平滑肌肌球蛋白基因产物包括两种亚型，SMA和SMB，不同之处在于肌球蛋白活性位点（ATP水解）的环1（i7）中的7个残基肽。使用鸡同种型，先前的工作表明，与插入i7的SMB相比，SMA中的i7缺失通过抑制核苷酸的活性位点进入和排出而抑制了强的肌动蛋白结合。此外，i7缺失抑制了与肌动蛋白激活的ATP酶中开关2闭合→打开转变相关的Pi释放。开关2远离环1，表明i7缺失对Pi释放具有变构效应。鸡SMA和SMB分别具有未知和稳健的核苷酸敏感性色氨酸（NST）荧光增量。人SMA和SMB都缺乏NST增量，而Ca 2 + ATP酶中的Pi释放不受i7缺失的影响。NST报告了开关2中构象变化后的中继螺旋运动，但处于开放→闭合转变中。NST是所有已知肌球蛋白亚型的共同点，但人平滑肌除外。对人SMA和SMB运动性的其他独立研究表明i7缺失没有功能性影响。平滑肌肌球蛋白是种属特异性肌球蛋白结构/功能差异的一个令人震惊的例子，强调了跨种属推断疾病相关突变体对肌球蛋白影响的危险。
Smooth muscle myosin gene products include two isoforms, SMA and SMB, differing by a 7‐residue peptide in loop 1 (i7) at the myosin active site where ATP is hydrolyzed. Using chicken isoforms, previous work indicated that the i7 deletion in SMA prolongs strong actin binding by inhibiting active site ingress and egress of nucleotide when compared to i7 inserted SMB. Additionally, i7 deletion inhibits Pi release associated with the switch 2 closed→open transition in actin‐activated ATPase. Switch 2 is far from loop 1 indicating i7 deletion has an allosteric effect on Pi release. Chicken SMA and SMB have unknown and robust nucleotide‐sensitive tryptophan (NST) fluorescence increments, respectively. Human SMA and SMB both lack NST increments while Pi release in Ca2+ATPase is not impacted by i7 deletion. The NST reports relay helix movement following conformation change in switch 2 but in the open→closed transition. The NST is common to all known myosin isoforms except human smooth muscle. Other independent works on human SMA and SMB motility indicate no functional effect of i7 deletion. Smooth muscle myosin is a stunning example of species‐specific myosin structure/function divergence underscoring the danger in extrapolating disease‐linked mutant effects on myosin across species.