Post-translational modifications of transporters.
Post-translational modifications of transporters.
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DOI：
10.1016/j.pharmthera.2018.06.013
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发表时间：
2018-12
影响因子：
13.5
通讯作者：
Swaan PW
中科院分区：
文献类型：
--
作者：
Czuba LC;Hillgren KM;Swaan PW
药物转运蛋白对于多种内源性化合物和外源性物质如激素、胆汁酸、肽、脂质、糖和药物的分布至关重要。存在两类药物转运蛋白-溶质载体（SLC）转运蛋白和ATP结合盒（ABC）转运蛋白-其主要区别在于用于跨膜屏障转运底物的能量来源。尽管药物转运蛋白具有疏水性并驻留在膜双层中，但其具有动态结构并在转运过程中采用许多构象。虽然有显着的文献证据的底物特异性和结构-功能关系的临床相关的药物转运蛋白，有一个较少的了解，在调节机制，有助于这些蛋白质的功能表达。翻译后修饰已被证明通过广泛的分子机制调节药物转运蛋白的功能表达。这些修饰通常通过在溶剂可接近的氨基酸残基上添加官能团（例如磷酸化）、小蛋白（例如泛素化）、糖链（例如糖基化）或脂质（例如棕榈酰化）而发生。这些共价添加通常作为信号级联的结果而发生，并且根据修饰的类型和信号事件的预期命运可能是可逆的。在这里，我们审查的重要作用，翻译后修饰有助于动态调节和功能的后果SLC和ABC药物转运蛋白，并强调最近的进展，了解其在转运蛋白的结构，功能和调节的作用。
Drug transporter proteins are critical to the distribution of a wide range of endogenous compounds and xenobiotics such as hormones, bile acids, peptides, lipids, sugars, and drugs. There are two classes of drug transporters– the solute carrier (SLC) transporters and ATP-binding cassette (ABC) transporters –which predominantly differ in the energy source utilized to transport substrates across a membrane barrier. Despite their hydrophobic nature and residence in the membrane bilayer, drug transporters have dynamic structures and adopt many conformations during the translocation process. Whereas there is significant literature evidence for the substrate specificity and structure-function relationship for clinically relevant drug transporters proteins, there is less of an understanding in the regulatory mechanisms that contribute to the functional expression of these proteins. Post-translational modifications have been shown to modulate drug transporter functional expression via a wide range of molecular mechanisms. These modifications commonly occur through the addition of a functional group (e.g. phosphorylation), a small protein (e.g. ubiquitination), sugar chains (e.g. glycosylation), or lipids (e.g. palmitoylation) on solvent accessible amino acid residues. These covalent additions often occur as a result of a signaling cascade and may be reversible depending on the type of modification and the intended fate of the signaling event. Here, we review the significant role in which post-translational modifications contribute to the dynamic regulation and functional consequences of SLC and ABC drug transporters and highlight recent progress in understanding their roles in transporter structure, function, and regulation.
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影响因子：
4.1
作者：
Chothe, Paresh P.;Swaan, Peter W.
通讯作者：
Swaan, Peter W.
由脂质力驱动的大量内吞作用，该脂质力源自外部浆膜单层：一种新的膜回收和脂质结构域的方法。
DOI：
10.1085/jgp.201010469
发表时间：
2011-02
期刊：
The Journal of general physiology
影响因子：
--
作者：
Fine M;Llaguno MC;Lariccia V;Lin MJ;Yaradanakul A;Hilgemann DW
通讯作者：
Hilgemann DW
影响因子：
3.6
作者：
Annamalai, Balasubramaniam;Mannangatti, Padmanabhan;Ramamoorthy, Sammanda
通讯作者：
Ramamoorthy, Sammanda
影响因子：
4.5
作者：
de Juan-Sanz, Jaime;Zafra, Francisco;Aragon, Carmen
通讯作者：
Aragon, Carmen
影响因子：
4.1
作者：
CHAMBERS, TC;POHL, J;KUO, JF
通讯作者：
KUO, JF