Kjaergaard Magnus, Kragelund Birthe B
Aarhus Institute of Advanced Studies (AIAS), Aarhus University, Aarhus, Denmark.
Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Cell Mol Life Sci. 2017 Sep;74(17):3205-3224. doi: 10.1007/s00018-017-2562-5. Epub 2017 Jun 10.
Intrinsic disorder is common in integral membrane proteins, particularly in the intracellular domains. Despite this observation, these domains are not always recognized as being disordered. In this review, we will discuss the biological functions of intrinsically disordered regions of membrane proteins, and address why the flexibility afforded by disorder is mechanistically important. Intrinsically disordered regions are present in many common classes of membrane proteins including ion channels and transporters; G-protein coupled receptors (GPCRs), receptor tyrosine kinases and cytokine receptors. The functions of the disordered regions are many and varied. We will discuss selected examples including: (1) Organization of receptors, kinases, phosphatases and second messenger sources into signaling complexes. (2) Modulation of the membrane-embedded domain function by ball-and-chain like mechanisms. (3) Trafficking of membrane proteins. (4) Transient membrane associations. (5) Post-translational modifications most notably phosphorylation and (6) disorder-linked isoform dependent function. We finish the review by discussing the future challenges facing the membrane protein community regarding protein disorder.
内在无序在整合膜蛋白中很常见，尤其是在细胞内结构域。尽管有这一观察结果，但这些结构域并不总是被认为是无序的。在本综述中，我们将讨论膜蛋白内在无序区域的生物学功能，并探讨无序所赋予的灵活性在机制上为何重要。内在无序区域存在于许多常见类型的膜蛋白中，包括离子通道和转运蛋白；G蛋白偶联受体（GPCR）、受体酪氨酸激酶和细胞因子受体。无序区域的功能多种多样。我们将讨论一些选定的例子，包括：（1） 将受体、激酶、磷酸酶和第二信使来源组织成信号复合物。（2） 通过球链样机制调节膜嵌入结构域的功能。（3） 膜蛋白的运输。（4） 瞬时膜关联。（5） 翻译后修饰，最显著的是磷酸化，以及（6） 与无序相关的异构体依赖性功能。我们通过讨论膜蛋白领域在蛋白质无序方面面临的未来挑战来结束本综述。
