Interactions of the C-terminus of lung surfactant protein B with lipid bilayers are modulated by acyl chain saturation.
Interactions of the C-terminus of lung surfactant protein B with lipid bilayers are modulated by acyl chain saturation.
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DOI：
10.1016/j.bbamem.2008.07.013
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发表时间：
2008-11
影响因子：
3.4
通讯作者：
Long, Joanna R.
中科院分区：
文献类型：
--
作者：
Antharam, Vijay C.;Farver, R. Suzanne;Kuznetsova, Anna;Sippel, Katherine H.;Mills, Frank D.;Elliott, Douglas W.;Sternin, Edward;Long, Joanna R.
肺表面活性蛋白B（SP-B）对于最小化肺泡中的表面张力至关重要。SP-B的C-末端，残基59-80，具有全蛋白质的大部分表面活性，并作为合成表面活性剂替代物开发的模板。负责其恢复肺顺应性的能力的分子机制进行了研究与圆二色性，差示扫描量热法，31 P和2 H固态NMR光谱。SP-B59-80形成两亲性螺旋，其改变流体层状相4：1 DPPC：POPG和3：1 POPC：POPG MLV中的脂质组织和酰基链动力学。在较高水平的SP-B59-80的POPC：POPG脂质系统中观察到的非层状相的过渡，而DPPC：POPG混合物保持在层状相。氘NMR显示，在添加SP-B59-80时，DPPC：POPG MLV中的酰基链序增加;在POPC：POPG MLV中，酰基链序参数降低。我们的研究结果表明SP-B59-80深深地渗透到DPPC：POPG双层中，并且更外围地结合到POPC：POPG双层。对于KL 4也观察到了类似的行为，KL 4是SP-B的肽模拟物，其最初是使用SP-B59-80作为模板设计的，并已在临床上证明成功治疗呼吸窘迫综合征。这些螺旋肽的能力，差异分区成脂质层含有不同水平的单不饱和度和随后的脂质动力学的变化表明，在动态肺环境中的脂质组织和贩运的机制。
Lung surfactant protein B (SP-B) is critical to minimizing surface tension in the alveoli. The C-terminus of SP-B, residues 59-80, has much of the surface activity of the full protein and serves as a template for the development of synthetic surfactant replacements. The molecular mechanisms responsible for its ability to restore lung compliance were investigated with circular dichroism, differential scanning calorimetry, and 31P and 2H solid-state NMR spectroscopy. SP-B59-80 forms an amphipathic helix which alters lipid organization and acyl chain dynamics in fluid lamellar phase 4:1 DPPC:POPG and 3:1 POPC:POPG MLVs. At higher levels of SP-B59-80 in the POPC:POPG lipid system a transition to a nonlamellar phase is observed while DPPC:POPG mixtures remain in a lamellar phase. Deuterium NMR shows an increase in acyl chain order in DPPC:POPG MLVs on addition of SP-B59-80; in POPC:POPG MLVs, acyl chain order parameters decrease. Our results indicate SP-B59-80 penetrates deeply into DPPC:POPG bilayers and binds more peripherally to POPC:POPG bilayers. Similar behavior has been observed for KL4, a peptide mimetic of SP-B which was originally designed using SP-B59-80 as a template and has been clinically demonstrated to be successful in treating respiratory distress syndrome. The ability of these helical peptides to differentially partition into lipid lamellae containing varying levels of monounsaturation and subsequent changes in lipid dynamics suggest a mechanism for lipid organization and trafficking within the dynamic lung environment.
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影响因子：
3.4
作者：
Abu-Baker, Shadi;Qi, Xiaoyang;Lorigan, Gary A.
通讯作者：
Lorigan, Gary A.
影响因子：
15
作者：
KULIOPULOS, A;WALSH, CT
通讯作者：
WALSH, CT
影响因子：
3.4
作者：
Ma, JW;Koppenol, S;Zografi, G
通讯作者：
Zografi, G
影响因子：
2.9
作者：
Booth, V;Waring, AJ;Keough, KMW
通讯作者：
Keough, KMW
DOI：
10.1073/pnas.88.16.7451
发表时间：
1991-08-01
影响因子：
11.1
作者：
BRUNI, R;TAEUSCH, HW;WARING, AJ
通讯作者：
WARING, AJ