Inhibition of TnI-TnC interaction and contraction of skinned muscle fibres by the synthetic peptide TnI [104–115]

Inhibition of TnI-TnC interaction and contraction of skinned muscle fibres by the synthetic peptide TnI [104–115]
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合成肽 TnI 抑制 TnI-TnC 相互作用和皮肤肌纤维收缩 [104–115]

DOI:
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发表时间:
1989
期刊:
Pflügers Archiv
影响因子:
--
通讯作者:
R. Hodges
R. Hodges
中科院分区:
--
文献类型:
--
作者:
J. Rüegg;C. Zeugner;J. Eyk;C. Kay;R. Hodges

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利用圆二色性研究了不同Ca2+浓度下TnI肽对TnC或TnI-TnC中螺旋的诱导作用[104-115]。肽-TnC复合物的负椭圆度和pCa2+值的增加表明肽与TnC的结合诱导了TnC的小螺旋构象变化。这导致Ca2+结合常数的增加和在TnC中诱导50% Ca2+依赖性螺旋所需的pCa50值。将多肽引入预先形成的TnI- tnc混合物中,导致负椭圆度增加,pCa50和表观Ca2+结合常数降低,趋近于TnI肽- tnc复合物的值,而远离TnI- tnc的值。这表明,TnI肽可以成功地与TnI竞争TnC,从而抑制TnI-TnC相互作用。将TnI肽添加到剥皮的兔腰大肌或猪心脏纤维中,可抑制力的发展,并降低50% Ca2+激活所需的pCa50值。张力发展的抑制程度和Ca2+敏感性的变化对剥皮心肌纤维大约是骨骼肌纤维观察到的一半。鉴于CD的发现,这些剥皮纤维的结果可以通过肽抑制TnI与TnC的相互作用来解释。然而,TnI肽也可能对TM-actin有直接抑制作用。另一种TnC结合肽Mastoparan也能抑制皮肤骨骼肌和心肌纤维的张力发展,但效果远不如TnI肽。
Circular dichroism was used to study the induction of helix in TnC or TnI-TnC by the TnI peptide [104–115] at various Ca2+ concentrations. The increase in negative ellipticity and pCa2+ values for the peptide-TnC complex, indicates that binding of the peptide to TnC, induces a small helical conformational change in TnC. This results in an increase in the Ca2+ binding constant and the pCa50 value required to induce 50% of Ca2+-dependent helix in TnC. The introduction of the peptide to a preformed mixture of TnI-TnC resulted in an increase in negative ellipticity and a decrease in the pCa50 and the apparent Ca2+ binding constant towards the values obtained for the TnI peptide-TnC complex and away from those of TnI-TnC. This demonstrates that the TnI peptide can successfully compete with TnI for TnC and thereby inhibit the TnI-TnC interaction. The addition of the TnI peptide to skinned rabbit psoas or porcine cardiac fibres resulted in the inhibition of the force development and a decrease in the pCa50 values required for 50% Ca2+ activation. The magnitude of the inhibition of tension development and the shift in the Ca2+ sensitivity for skinned cardiac muscle fibres was approximately half that observed with skeletal muscle fibres. In view of the CD findings, these skinned fibre results can be accounted for by the peptide inhibiting the TnI interaction with TnC. However, it is possible that the TnI peptide also has a direct inhibitory effect on TM-actin. Mastoparan, another TnC binding peptide, also inhibited the tension development in skinned skeletal and cardiac muscle fibres, but was much less efficient than the TnI peptide.
DOI: 10.1016/s0021-9258(19)70187-2
发表时间: 1980-12
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影响因子: --
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DOI: --
发表时间: 1986
期刊: The Journal of biological chemistry
影响因子: --
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