Kozlov Guennadi, Wong Kathy, Wang Wenxuan, Skubák Pavol, Muñoz-Escobar Juliana, Liu Yue, Siddiqui Nadeem, Pannu Navraj S, Gehring Kalle
Department of Biochemistry, Groupe de recherche axé sur la structure des protéines, McGill University, Montreal, QC H3G 0B1, Canada.
Biophysical Structural Chemistry, Leiden University, 2300 RA Leiden, The Netherlands.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):1002-1007. doi: 10.1016/j.bbrc.2017.11.135. Epub 2017 Nov 21.
Legionella pneumophila is a pathogen, causing severe pneumonia in humans called Legionnaires' disease. AnkC (LegA12) is a poorly characterized 495-residue effector protein conserved in multiple Legionella species. Here, we report the crystal structure of a C-terminally truncated AnkC (2-384) at 3.2 Å resolution. The structure shows seven ankyrin repeats (ARs) with unique structural features. AnkC forms a dimer along the outer surface of loops between ARs. The dimer exists both in the crystal form and in solution, as shown by analytical ultracentrifugation. This is the first example of ARs as a dimerization module as opposed to solely a protein interaction domain. In addition, a novel α-helix insert between AR3-AR4 is positioned across the surface opposite the ankyrin groove. Sequence conservation suggests that the ankyrin groove of AnkC is a functional site that interacts with binding targets. This ankyrin domain structure is an important step towards a functional characterization of AnkC.
嗜肺军团菌是一种病原体，可导致人类患上严重肺炎，即军团病。AnkC（LegA12）是一种在多种军团菌物种中保守的、特征描述较少的495个氨基酸残基的效应蛋白。在此，我们报告了C端截短的AnkC（2-384）在3.2埃分辨率下的晶体结构。该结构显示出具有独特结构特征的七个锚蛋白重复序列（ARs）。AnkC沿着ARs之间环的外表面形成二聚体。如分析超速离心所示，二聚体以晶体形式和溶液形式存在。这是ARs作为二聚化模块而非仅仅作为蛋白质相互作用结构域的首个例子。此外，AR3-AR4之间的一个新型α-螺旋插入片段位于与锚蛋白凹槽相对的表面上。序列保守性表明AnkC的锚蛋白凹槽是与结合靶点相互作用的功能位点。这种锚蛋白结构域结构是对AnkC进行功能表征的重要一步。
