Sequence-specific conformational dynamics of model transmembrane domains determines their membrane fusogenic function.
Sequence-specific conformational dynamics of model transmembrane domains determines their membrane fusogenic function.
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模型跨膜域的序列特异性构象动力学决定了它们的膜融合功能。
DOI：
10.1016/j.jmb.2008.12.077
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发表时间：
2009
影响因子：
5.6
通讯作者：
D. Langosch
中科院分区：
文献类型：
--
作者：
Bernhard C. Poschner;Stefan Quint;Mathias W. Hofmann;D. Langosch
已知融合蛋白的跨膜结构域具有重要的功能，并且显示出过多的螺旋不稳定 Ile 和 Val 残基。为了系统地研究融合性和螺旋稳定性的关系，我们之前设计了 LV 肽，这是一种低复杂性模型系统，其疏水核心由不同比例的 Leu 和 Val 残基组成。 LV 肽融合膜的能力随着螺旋不稳定残基的含量而增加。在这里，我们监测了 LV 肽螺旋的酰胺氘/氢交换动力学，以探测其构象动力学。动力学确实随着螺旋不稳定残基的含量而强烈增加，并且可能反映了螺旋主链的局部波动，因为所有肽都表现出不相关的交换并且包含以不同速度交换的酰胺氘原子亚群。有趣的是，酰胺氘原子从较慢的亚群转移到较快的亚群的螺旋更具融合性。 Val 残基集中在疏水核心的外围或中心结构域的新型肽变体被设计用于绘制功能相关的螺旋子结构域。他们的结构和功能分析表明，靠近螺旋末端的动态域比中心域与融合性更相关，但与后者配合以实现强融合性。
The transmembrane domains of fusion proteins are known to be functionally important and display an overabundance of helix-destabilizing Ile and Val residues. In an effort to systematically study the relationship of fusogenicity and helix stability, we previously designed LV peptides, a low-complexity model system whose hydrophobic core consists of Leu and Val residues at different ratios. The ability of LV peptides to fuse membranes increases with the content of helix-destabilizing residues. Here, we monitored the kinetics of amide deuterium/hydrogen exchange of LV-peptide helices to probe their conformational dynamics. The kinetics indeed increases strongly with the content of helix-destabilizing residues and is likely to reflect local fluctuations of the helix backbones as all peptides exhibit uncorrelated exchange and contain subpopulations of amide deuterium atoms that exchange with different velocities. Interestingly, helices whose amide deuterium atoms are shifted from slower to faster subpopulations are more fusogenic. Novel peptide variants in which Val residues are concentrated at peripheral or central domains of the hydrophobic core were designed to map functionally relevant helix subdomains. Their structural and functional analysis suggests that dynamic domains close to the helix termini are more relevant for fusogenicity than central domains but cooperate with the latter to achieve strong fusogenicity.
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影响因子：
5.6
作者：
Langosch, D;Crane, JM;Reed, J
通讯作者：
Reed, J
影响因子：
2.9
作者：
SUBCZYNSKI, WK;WISNIEWSKA, A;KUSUMI, A
通讯作者：
KUSUMI, A
影响因子：
56.9
作者：
BLABER, M;ZHANG, XJ;MATTHEWS, BW
通讯作者：
MATTHEWS, BW
DOI：
10.1073/pnas.89.13.5937
发表时间：
1992-07-01
影响因子：
11.1
作者：
CREAMER, TP;ROSE, GD
通讯作者：
ROSE, GD
细胞色素 c 的二维 1H NMR 研究：N 末端螺旋中的氢交换。
影响因子：
2.9
作者：
Wand,AJ;Roder,H;Englander,SW
通讯作者：
Englander,SW