Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas, USA.
J Bacteriol. 2013 Jul;195(13):3022-34. doi: 10.1128/JB.00287-13. Epub 2013 Apr 26.
The Agrobacterium tumefaciens VirB/VirD4 type IV secretion system is composed of a translocation channel and an extracellular T pilus. Bitopic VirB10, the VirB7 lipoprotein, and VirB9 interact to form a cell envelope-spanning structural scaffold termed the "core complex" that is required for the assembly of both structures. The related pKM101-encoded core complex is composed of 14 copies each of these VirB homologs, and the transmembrane (TM) α helices of VirB10-like TraF form a 55-Å-diameter ring at the inner membrane. Here, we report that the VirB10 TM helix possesses two types of putative dimerization motifs, a GxxxA (GA4) motif and two leucine (Leu1, Leu2) zippers. Mutations in the Leu1 motif disrupted T-pilus biogenesis, but these or other mutations in the GA4 or Leu2 motif did not abolish substrate transfer. Replacement of the VirB10 TM domain with a nondimerizing poly-Leu/Ala TM domain sequence also blocked pilus production but not substrate transfer or formation of immunoprecipitable complexes with the core subunits VirB7 and VirB9 and the substrate receptor VirD4. The VirB10 TM helix formed weak homodimers in Escherichia coli, as determined with the TOXCAT assay, whereas replacement of the VirB10 TM helix with the strongly dimerizing TM helix from glycophorin A blocked T-pilus biogenesis in A. tumefaciens. Our findings support a model in which VirB10's TM helix contributes to the assembly or activity of the translocation channel as a weakly self-interacting membrane anchor but establishes a heteromeric TM-TM helix interaction via its Leu1 motif that is critical for T-pilus biogenesis.
农杆菌 VirB/VirD4 型 IV 型分泌系统由一个转位通道和一个细胞外 T 菌毛组成。双位 VirB10、VirB7 脂蛋白和 VirB9 相互作用形成一个细胞包膜贯穿的结构支架,称为“核心复合物”,这是组装这两种结构所必需的。相关的 pKM101 编码的核心复合物由这些 VirB 同源物的每个 14 个拷贝组成,并且 VirB10 样 TraF 的跨膜 (TM) α 螺旋在内膜形成一个 55 Å 直径的环。在这里,我们报告 VirB10 TM 螺旋具有两种类型的假定二聚化基序,一个 GxxxA(GA4)基序和两个亮氨酸(Leu1、Leu2)拉链。Leu1 基序中的突变破坏了 T-菌毛的生物发生,但这些或 GA4 或 Leu2 基序中的其他突变并没有消除底物转移。用非二聚化的多亮氨酸/丙氨酸 TM 结构域序列替换 VirB10 TM 结构域也阻断了菌毛的产生,但不阻断底物转移或与核心亚基 VirB7 和 VirB9 以及底物受体 VirD4 形成可免疫沉淀的复合物。通过 TOXCAT 测定,在大肠杆菌中,VirB10 TM 螺旋形成弱同源二聚体,而用强烈二聚化的糖蛋白 A TM 螺旋替换 VirB10 TM 螺旋则阻止了农杆菌中 T-菌毛的生物发生。我们的发现支持这样一种模型,即 VirB10 的 TM 螺旋作为一个弱自相互作用的膜锚定物有助于转位通道的组装或活性,但通过其 Leu1 基序建立一个异源 TM-TM 螺旋相互作用,这对于 T-菌毛的生物发生至关重要。