Lau Tong-Lay, Partridge Anthony W, Ginsberg Mark H, Ulmer Tobias S
Department of Biochemistry and Molecular Biology and Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, 1501 San Pablo Street, Los Angeles, California 90033, USA.
Biochemistry. 2008 Apr 1;47(13):4008-16. doi: 10.1021/bi800107a. Epub 2008 Mar 6.
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 beta3 integrin transmembrane segment and flanking sequences were carried out in both phospholipid bicelles and detergent micelles. In bicelles, a 30-residue linear alpha-helix, encompassing residues I693-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 beta3 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 beta3 transmembrane segment. In the micelle, residues L717-I721 are also embedded but deviate from linear alpha-helical conformation in contrast to I693-K716, which closely resemble the bicelle structure.
整合素黏附受体在质膜上双向传导信号，在此过程中整合素跨膜结构域充当信号传导通道。在此，我们报道了整合素跨膜结构域的首个高分辨率结构。为评估膜模型系统的影响，我们在磷脂双分子层和去污剂胶束中对β3整合素跨膜片段及其侧翼序列进行了结构测定。在双分子层中，形成了一个包含I693 - H772残基的30个残基的线性α螺旋，其中I693 - I721似乎嵌入疏水双分子层核心。这种相对较长的跨膜螺旋意味着在典型脂质双层内有明显的螺旋倾斜，这有利于K716带电荷的侧链从脂质核心中“ snorkeling ”出来，同时将疏水的L717 - I721浸入膜中。缩短双分子层脂质烃链尾部并不会导致L717 - I721转移到水相中，这表明所报道的嵌入状态代表了β3的优选状态。脂质头部基团的性质仅影响跨膜螺旋的细胞内部分，这表明研究β3跨膜片段不需要不对称的脂质分布。在胶束中，L717 - I721残基也被嵌入，但与紧密类似于双分子层结构的I693 - K716不同，它们偏离了线性α螺旋构象。
