Fungal PDR transporters: Phylogeny, topology, motifs and function.

Fungal PDR transporters: Phylogeny, topology, motifs and function.
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DOI:
10.1016/j.fgb.2009.10.007
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发表时间:
2010-02
影响因子:
3
通讯作者:
Cannon, Richard D.
Cannon, Richard D.
中科院分区:
生物学3区
文献类型:
--
作者:
Lamping, Erwin;Baret, Philippe V.;Holmes, Ann R.;Monk, Brian C.;Goffeau, Andre;Cannon, Richard D.

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三磷酸腺苷结合盒(ABC)转运体超家族多效性耐药(PDR)外排泵的过度表达与多药耐药密切相关。对包括主要病原菌在内的55种真菌的349个全长(~160 kDa)的PDR蛋白进行了系统发育分析,确定了9个独立的蛋白质簇(A、B、C、D、E、F、G、H1a/H1B和H2)。真菌、植物和人类ABCG家族的PSRPs具有一个核苷酸结合结构域[NBD]和一个跨膜结构域[TMD],该结构域在家族定义的‘反向’ABC转运蛋白拓扑结构[NBD-TMD]中被复制[NBD-TMD]2。虽然全尺寸的PSRPs有相似的一半指示早期基因复制/融合,但它们表现出NBD和胞外环(ELs)的不对称。簇F的成员是最对称的,可能与Pdrp的进化祖先密切相关。预测了独特的结构元素,识别了新的PDR特定基序,并讨论了这些和其他结构特征的意义。
The overexpression of pleiotropic drug resistance (PDR) efflux pumps of the ATP-binding cassette (ABC) transporter superfamily frequently correlates with multidrug resistance. Phylogenetic analysis of 349 full-size (~160 kDa) PDR proteins (Pdrps) from 55 fungal species, including major fungal pathogens, identified 9 separate protein clusters (A, B, C, D, E, F, G, H1a/H1b and H2). Fungal, plant and human ABCG-family Pdrps possess a nucleotide-binding domain [NBD] and a transmembrane domain [TMD] in a family-defining ‘reverse’ ABC transporter topology [NBD-TMD] that is duplicated [NBD-TMD]2 in full-size fungal and plant Pdrps [NBD-TMD]2. Although full-size Pdrps have similar halves indicating early gene duplication/fusion, they show asymmetry of their NBDs and extracellular loops (ELs). Members of cluster F are most symmetric and may be closely related to the evolutionary ancestor of Pdrps. Unique structural elements are predicted, new PDR-specific motifs identified, and the significance of these and other structural features discussed.
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