Structural Basis of Host Autophagy-related Protein 8 (ATG8) Binding by the Irish Potato Famine Pathogen Effector Protein PexRD54.

Structural Basis of Host Autophagy-related Protein 8 (ATG8) Binding by the Irish Potato Famine Pathogen Effector Protein PexRD54.
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DOI:
10.1074/jbc.m116.744995
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发表时间:
2016-09-16
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
Banfield MJ
Banfield MJ
中科院分区:
其他
文献类型:
--
作者:
Maqbool A;Hughes RK;Dagdas YF;Tregidgo N;Zess E;Belhaj K;Round A;Bozkurt TO;Kamoun S;Banfield MJ

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丝状植物病原体将效应蛋白运送到宿主细胞以促进感染。致病疫霉RXLR型效应子PexRD54通过其ATG8家族相互作用基序(AIM)与马铃薯ATG8结合,干扰宿主选择性自噬。然而,这种相互作用的结构基础仍然未知。在这里,我们定义了PexRD54的晶体结构,它包括一个模块化的结构,包括五个串联重复结构域,AIM序列出现在无序的C末端。为了确定PexRD54和ATG8之间的界面,我们用含有效应子AIM序列的多肽解算了马铃薯ATG8CL的晶体结构,并用小角X射线散射建立了全长PexRD54-ATG8CL的模型。PexRD54串联结构域的结构信息删除表明ATG8CL在体外和植物中的结合被保留。这项研究为卵菌RXLR效应器的结构/功能关系以及这些蛋白如何与宿主细胞靶标接触以促进疾病提供了新的见解。
Filamentous plant pathogens deliver effector proteins to host cells to promote infection. The Phytophthora infestans RXLR-type effector PexRD54 binds potato ATG8 via its ATG8 family-interacting motif (AIM) and perturbs host-selective autophagy. However, the structural basis of this interaction remains unknown. Here, we define the crystal structure of PexRD54, which includes a modular architecture, including five tandem repeat domains, with the AIM sequence presented at the disordered C terminus. To determine the interface between PexRD54 and ATG8, we solved the crystal structure of potato ATG8CL in complex with a peptide comprising the effector's AIM sequence, and we established a model of the full-length PexRD54-ATG8CL complex using small angle x-ray scattering. Structure-informed deletion of the PexRD54 tandem domains reveals retention of ATG8CL binding in vitro and in planta. This study offers new insights into structure/function relationships of oomycete RXLR effectors and how these proteins engage with host cell targets to promote disease.