Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.

Crystal structures of Cif from bacterial pathogens Photorhabdus luminescens and Burkholderia pseudomallei.
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DOI:
10.1371/journal.pone.0005582
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发表时间:
2009
期刊:
影响因子:
3.7
通讯作者:
Banfield MJ
Banfield MJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Crow A;Race PR;Jubelin G;Varela Chavez C;Escoubas JM;Oswald E;Banfield MJ

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细菌发病的先决条件是病原体与宿主的成功相互作用。广泛的革兰氏阴性细菌病原体使用的一种机制是通过专门的III型分泌系统将效应蛋白直接输送到宿主细胞中,在那里它们调节宿主细胞的功能。周期抑制因子(Cif)家族效应蛋白在越来越多的病原体中被发现,这些病原体具有功能III型分泌系统并且具有广泛的宿主范围,可以阻止真核细胞周期。本文介绍了昆虫病原体/线虫共生体光habdus luminescens(一种γ-变形菌)和人类病原体假马勒伯克氏菌(一种β-变形菌)中Cifs的晶体结构。这两种蛋白的整体折叠与半胱氨酸蛋白酶的木瓜蛋白酶亚家族相似,最初在肠致病性大肠杆菌(EPEC)的Cif的截短形式的结构中发现,尽管只有有限的序列相同。n端区域的结构,在这里被称为“尾域”(在EPEC Cif结构中不存在),表明可能参与宿主细胞底物识别的表面。Cys-His-Gln催化三联体的构象被保留,必需的半胱氨酸暴露在溶剂中,可被小分子试剂寻址。这些结构和生物化学方面的工作有助于快速扩展有关Cifs的文献,并指导进一步的研究,以更好地了解这些蛋白质活性的分子细节。
A pre-requisite for bacterial pathogenesis is the successful interaction of a pathogen with a host. One mechanism used by a broad range of Gram negative bacterial pathogens is to deliver effector proteins directly into host cells through a dedicated type III secretion system where they modulate host cell function. The cycle inhibiting factor (Cif) family of effector proteins, identified in a growing number of pathogens that harbour functional type III secretion systems and have a wide host range, arrest the eukaryotic cell cycle. Here, the crystal structures of Cifs from the insect pathogen/nematode symbiont Photorhabdus luminescens (a γ-proteobacterium) and human pathogen Burkholderia pseudomallei (a β-proteobacterium) are presented. Both of these proteins adopt an overall fold similar to the papain sub-family of cysteine proteases, as originally identified in the structure of a truncated form of Cif from Enteropathogenic E. coli (EPEC), despite sharing only limited sequence identity. The structure of an N-terminal region, referred to here as the ‘tail-domain’ (absent in the EPEC Cif structure), suggests a surface likely to be involved in host-cell substrate recognition. The conformation of the Cys-His-Gln catalytic triad is retained, and the essential cysteine is exposed to solvent and addressable by small molecule reagents. These structures and biochemical work contribute to the rapidly expanding literature on Cifs, and direct further studies to better understand the molecular details of the activity of these proteins.
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发表时间: 2008-12-12
影响因子: 5.6
作者:
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