Insights into the key determinants of membrane protein topology enable the identification of new monotopic folds.
Insights into the key determinants of membrane protein topology enable the identification of new monotopic folds.
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DOI：
10.7554/elife.40889
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发表时间：
2018-08-31
期刊：
影响因子：
7.7
通讯作者：
Imperiali B
中科院分区：
文献类型：
--
作者：
Entova S;Billod JM;Swiecicki JM;Martín-Santamaría S;Imperiali B
单配体膜蛋白通过在膜的单面上进入和离开的可重入疏水结构域整合到脂质双层中。虽然许多跨膜蛋白的结构特征和跨膜拓扑结构可以预测计算，相对知之甚少的决定因素，膜拓扑结构的单调蛋白质。最近，我们报道了具有磷酸糖基转移酶（PGT）活性的全长单调膜蛋白PglC的X射线结构测定。这种独特的结构的定义，促使在体内，生物化学和计算分析，以了解和定义的关键图案，有助于膜的拓扑结构，并提供洞察酶的动态在脂质双层环境。使用从PGT超家族的研究中获得的新信息，我们证明了两个基序的拓扑结构确定的原则，可以应用于识别不同的单调感兴趣的蛋白质之间的折返结构域。
Monotopic membrane proteins integrate into the lipid bilayer via reentrant hydrophobic domains that enter and exit on a single face of the membrane. Whereas many membrane-spanning proteins have been structurally characterized and transmembrane topologies can be predicted computationally, relatively little is known about the determinants of membrane topology in monotopic proteins. Recently, we reported the X-ray structure determination of PglC, a full-length monotopic membrane protein with phosphoglycosyl transferase (PGT) activity. The definition of this unique structure has prompted in vivo, biochemical, and computational analyses to understand and define key motifs that contribute to the membrane topology and to provide insight into the dynamics of the enzyme in a lipid bilayer environment. Using the new information gained from studies on the PGT superfamily we demonstrate that two motifs exemplify principles of topology determination that can be applied to the identification of reentrant domains among diverse monotopic proteins of interest.