Role of the N-terminal seven residues of surfactant protein B (SP-B).

Role of the N-terminal seven residues of surfactant protein B (SP-B).
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DOI:
10.1371/journal.pone.0072821
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Booth V
Booth V
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sharifahmadian M;Sarker M;Palleboina D;Waring AJ;Walther FJ;Morrow MR;Booth V

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呼吸是通过肺表面活性剂实现的,肺表面活性剂是蛋白质和脂质的混合物,形成表面活性层并降低肺中空气-水界面的表面张力。表面活性蛋白B(SP-B)是肺表面活性物质的重要组成部分。在本研究中,我们探讨了 SP-B N 端 7 个残基(有时称为“插入序列”的区域)做出重要功能贡献的机制。这些研究采用了 SP-B 的构建体,SP-B (1–25,63–78),也称为 Super Mini-B,它是一种具有内部二硫键的 41 个残基肽,包含 N 端 7 个残基插入序列以及 SP-B 的 N 端和 C 端螺旋。使用圆二色性、溶液 NMR 和固态 2H NMR 研究 SP-B (1–25,63–78) 的结构及其与磷脂双层的相互作用。 SP-B (8-25,63-78) 和 SP-B (1-25,63-78) 结果的比较表明,7 个残基插入序列的存在会引起脂质双层中心附近的严重紊乱,但不会严重破坏双层的整体机械方向。这一观察结果表明插入序列不太可能深入渗透到双层中。 7 个残基插入序列大大增加了溶液 NMR 线宽,这很可能是由于全局动力学的增加。
Breathing is enabled by lung surfactant, a mixture of proteins and lipids that forms a surface-active layer and reduces surface tension at the air-water interface in lungs. Surfactant protein B (SP-B) is an essential component of lung surfactant. In this study we probe the mechanism underlying the important functional contributions made by the N-terminal 7 residues of SP-B, a region sometimes called the “insertion sequence”. These studies employed a construct of SP-B, SP-B (1–25,63–78), also called Super Mini-B, which is a 41-residue peptide with internal disulfide bonds comprising the N-terminal 7-residue insertion sequence and the N- and C-terminal helices of SP-B. Circular dichroism, solution NMR, and solid state 2H NMR were used to study the structure of SP-B (1–25,63–78) and its interactions with phospholipid bilayers. Comparison of results for SP-B (8–25,63–78) and SP-B (1–25,63–78) demonstrates that the presence of the 7-residue insertion sequence induces substantial disorder near the centre of the lipid bilayer, but without a major disruption of the overall mechanical orientation of the bilayers. This observation suggests the insertion sequence is unlikely to penetrate deeply into the bilayer. The 7-residue insertion sequence substantially increases the solution NMR linewidths, most likely due to an increase in global dynamics.
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