Structure of the integrin β3 transmembrane segment in phospholipid bicelles and detergent micelles
Structure of the integrin β3 transmembrane segment in phospholipid bicelles and detergent micelles
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DOI：
10.1021/bi800107a
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发表时间：
2008-04-01
期刊：
影响因子：
2.9
通讯作者：
Ulmer, Tobias S.
中科院分区：
文献类型：
--
作者：
Lau, Tong-Lay;Partridge, Anthony W.;Ulmer, Tobias S.
整合素粘附受体在质膜上传递双向信号，而整合素跨膜结构域在这一过程中起着管道的作用。在此，我们首次报告了整合素跨膜结构域的高分辨率结构。为了评估膜模型系统的影响，我们在磷脂双细胞和洗涤剂胶束中对 3 个整合素跨膜片段和侧翼序列进行了结构测定。在双细胞中，采用了 30 个残基的线性 cc-螺旋，包括残基 1693-H772，其中 I693-I721 出现在疏水性双细胞核心中。这种相对较长的跨膜螺旋意味着在典型的脂质双分子层中有明显的螺旋倾斜，这有利于 K716 的带电侧链潜出脂质核心，同时将疏水性的 L717-I721 浸入膜中。双胶束脂质碳氢化合物尾部的缩短不会导致 L717-I721 转移到水相，这表明所报告的嵌入代表了首选的 3 态。脂质头基的性质只影响跨膜螺旋的胞内部分，这表明研究 3 跨膜片段并不需要不对称的脂质分布。在胶束中，残基 L717-I721 也被嵌入，但偏离了线性 cc 螺旋构象，而 I693-K716 与双胶束结构非常相似。
Integrin adhesion receptors transduce bidirectional signals across the plasma membrane, with the integrin transmembrane domains acting as conduits in this process. Here, we report the first high-resolution structure of an integrin transmembrane domain. To assess the influence of the membrane model system, structure determinations of the 3 integrin transmembrane segment and flanking sequences were carried out in both phospholipid bicelles and detergent micelles. In bicelles, a 30-residue linear cc-helix, encompassing residues 1693-H772, is adopted, of which I693-I721 appear embedded in the hydrophobic bicelle core. This relatively long transmembrane helix implies a pronounced helix tilt within a typical lipid bilayer, which facilitates the snorkeling of K716's charged side chain out of the lipid core while simultaneously immersing hydrophobic L717-I721 in the membrane. A shortening of bicelle lipid hydrocarbon tails does not lead to the transfer of L717-I721 into the aqueous phase, suggesting that the reported embedding represents the preferred 3 state. the nature of the lipid headgroup affected only the intracellular part of the transmembrane helix, indicating that an asymmetric lipid distribution is not required for studying the 3 transmembrane segment. In the micelle, residues L717-I721 are also embedded but deviate from linear cc-helical conformation in contrast to I693-K716, which closely resemble the bicelle structure.