Structural characterization of the caveolin scaffolding domain in association with cholesterol-rich membranes.
Structural characterization of the caveolin scaffolding domain in association with cholesterol-rich membranes.
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DOI：
10.1021/bi201356v
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发表时间：
2012-01-10
期刊：
影响因子：
2.9
通讯作者：
van der Wel, Patrick C. A.
中科院分区：
文献类型：
--
作者：
Hoop, Cody L.;Sivanandam, V. N.;Kodali, Ravindra;Srnec, Matthew N.;van der Wel, Patrick C. A.
小窝蛋白家族成员参与小窝的形成，并在许多信号通路和各种蛋白质的调节中发挥重要作用。我们使用互补光谱方法研究了小窝蛋白-1片段中小窝蛋白支架结构域(CSD)的结构，同时结合到富含胆固醇的膜上。这个关键结构域被认为参与了多种关键功能，包括蛋白质识别、寡聚和胆固醇结合。在我们的膜结合肽中，发现侧翼膜内结构域中的残基采用α-螺旋结构，与人们普遍认为的螺旋发夹构象一致。有趣的是，在这些相同的多肽中，我们观察到CSD中残基的β链构象，而以前的报道通常不反映β结构。我们基于固体核磁共振、CD和FTIR的实验数据与一级序列二级结构择优的计算分析是一致的。我们讨论了我们的膜结合Cav片段的结构数据如何与胆固醇结合结构域的某些一般特征相匹配，并与CSD在蛋白质识别和同源齐聚中的作用相一致。
Members of the caveolin protein family are implicated in the formation of caveolae and play important roles in a number of signaling pathways and in the regulation of various proteins. We employ complementary spectroscopic methods to study the structure of the caveolin scaffolding domain (CSD) in caveolin-1 fragments, while bound to cholesterol-rich membranes. This key domain is thought to be involved in multiple critical functions that include protein recognition, oligomerization, and cholesterol binding. In our membrane-bound peptides, residues within the flanking intramembrane domain (IMD) are found to adopt an α-helical structure, consistent with its commonly believed helical hairpin conformation. Intriguingly, in these same peptides, we observe a β-stranded conformation for residues in the CSD, contrasting with earlier reports, which commonly do not reflect β-structure. Our experimental data based on solid-state NMR, CD, and FTIR are found to be consistent with computational analyses of the secondary structure preference of the primary sequence. We discuss how our structural data of membrane binding Cav fragments may match certain general features of cholesterol-binding domains and could be consistent with the role for CSD in protein recognition and homo-oligomerization.
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